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GENE:

PALB2 (Partner and localizer of BRCA2)

i
Other names: PALB2, Partner And Localizer Of BRCA2, FANCN, Truncated Partner And Localizer Of BRCA2, Fanconi Anemia, Complementation Group N, Mutant Partner And Localizer Of BRCA2, PNCA3
4d
Proline variants in the BRCA1 coiled-coil domain disrupt folding and binding to PALB2. (PubMed, Protein Sci)
Structural analysis indicates that all BRCA1 mutations to proline tested disrupt α-helix formation and therefore are not well tolerated even when located at positions outside of the PALB2-binding interface. This assay and the structural hypothesis described will be helpful for assessing risk for variants identified in the future in the BRCA1/PALB2 interaction domains.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • PALB2 (Partner and localizer of BRCA2)
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BRCA1 mutation • PALB2 mutation
5d
Population-based germline testing of BRCA1, BRCA2, and PALB2 in breast cancer patients in the United Kingdom: Evidence to support extended testing, and definition of groups who may not require testing. (PubMed, Genet Med Open)
The best strategy to detect all PVs was an MS ≥3 with specificity of 32.6%. In order to detect higher PV rates on a population basis the best strategy is to reduce the MS threshold for genetic testing.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset)
5d
Combining rare and common genetic variants improves population risk stratification for breast cancer. (PubMed, Genet Med Open)
Moreover, women with a pLOF in ATM or CHEK2 and ranking in the top 50% of the PRS displayed a high risk (39.2% probability of breast cancer at age 70), whereas their counterparts in the bottom 50% of the PRS were not at high risk (14.4% probability at age 70). Our findings suggest that a combined monogenic and polygenic approach allowed a better identification of participants with high risk while minimizing false positives.
Journal
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
5d
Cancer burden in individuals with single versus double pathogenic variants in cancer susceptibility genes. (PubMed, Genet Med Open)
Individuals with ATM+CHEK2 or 2 CHEK2 PVs have a greater cancer burden than single gene controls. These findings can be used to counsel individuals with DPVs and their families and inform cancer screening recommendations.
Journal
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
5d
Combined bioinformatic and splicing analysis of likely benign intronic and synonymous variants reveals evidence for pathogenicity. (PubMed, Genet Med Open)
When available, phenotypic information from submitting laboratories demonstrated DICER1-associated tumors in 2 families (1 variant) and breast cancer in 3 families (2 PALB2 variants). Incorporation of SpliceAI in variant curation pipelines may improve classification of B/LB intronic and synonymous variants and highlight putative pathogenic variants for functional assays and RNA analysis, thereby increasing diagnostic yield for rare diseases.
Journal
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PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • DICER1 (Dicer 1 Ribonuclease III)
6d
Prevalence and Distribution of Unexpected Actionable Germline Pathogenic Variants Identified on Broad-Based Multigene Panel Testing Among Patients With Cancer. (PubMed, JCO Precis Oncol)
In patients with cancer, MGPT identified a rate of 1.7% PV in unexpected actionable cancer predisposition genes. Findings were more often unexpected (2.8%) when considering only the patient cancer history. These findings may justify consideration of broader MGPT panels in patients with cancer, given implications for subsequent surveillance, cascade testing, and treatment options dependent on specific findings.
Retrospective data • Journal • BRCA Biomarker
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TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MSH6 (MutS homolog 6) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • MITF (Melanocyte Inducing Transcription Factor) • SDHC (Succinate Dehydrogenase Complex Subunit C) • HOXB13 (Homeobox B13) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
6d
Four pathogenic variants co-occurring in a MINAS early-onset breast cancer. (PubMed, Tumori)
Currently, there are no predictive tools available to determine organ-specific cancer risk in MINAS patients. Given the uncertainty in predicting the phenotypic effect of multiple variants in CSGs, ongoing clinical surveillance and sharing data from complex cases are crucial for improving risk stratification in this condition.
Journal
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PALB2 (Partner and localizer of BRCA2) • PMS2 (PMS1 protein homolog 2) • MUTYH (MutY homolog)
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PALB2 mutation
7d
Response to Carboplatin and Paclitaxel in the treatment of hereditary breast ovarian cancer syndrome (HBOC): a case report. (PubMed, J Pak Med Assoc)
This dynamic treatment not only led to nearly complete remission of high-grade ovarian serous cancer but also triggered regression in grade-2 invasive ductal breast cancer after just a few rounds of chemotherapy. Consequently, what started as palliative care evolved into a curative triumph.
Journal • BRCA Biomarker
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1)
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TP53 mutation • BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CHEK1 mutation • CHEK1 expression
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carboplatin • paclitaxel
12d
A phase II study evaluating safety and efficacy of niraparib in patients with previously treated homologous recombination defective metastatic esophageal/gastroesophageal junction/proximal gastric adenocarcinoma. (PubMed, Front Oncol)
The most common adverse events seen were anemia, fatigue, and thrombocytopenia. In patients with metastatic EAC, single agent niraparib as second line therapy is not an effective option.
P2 data • Journal • Metastases
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • GEN1 (GEN1 Holliday junction 5' flap endonuclease) • PARP2 (Poly(ADP-Ribose) Polymerase 2)
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FANCA deletion
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Zejula (niraparib)
12d
Severe Radiation-Induced Brachial Plexopathy: A Case Report on Radiation Toxicity in a Patient With Invasive Ductal Carcinoma. (PubMed, Cureus)
Here, we present a case of a 50-year-old woman with stage IIIA invasive ductal carcinoma of the left breast who had genetic testing revealing pathogenic ATM mutations (c.5290del and c.4396C>G) and a PALB2 mutation (c.1619dup). While guidelines suggest that adjuvant radiation therapy is safe for patients with ATM mutations, this patient experienced severe radiation-induced toxicities, including brachial plexopathy. These ATM mutations have not previously been described as imparting severe radiation-associated toxicities.
Journal
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ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2)
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PALB2 mutation
21d
Should We Offer Universal Germline Genetic Testing to All Patients with Pancreatic Cancer? A Multicenter Study. (PubMed, Cancers (Basel))
In our PDAC cohort, a noteworthy number of GPVs were identified, and half of these patients would have been classified as sporadic based solely on clinical criteria. Genetic testing should always be considered, particularly in patients under 60 years or those with a history of other malignancies, especially where economic resources need optimization.
Clinical • Journal • BRCA Biomarker
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TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)
22d
Novel Therapies for Pancreatic Cancer. (PubMed, JCO Oncol Pract)
Combination chemotherapy regimens using fluorouracil (fluorouracil, oxaliplatin, leucovorin, and irinotecan; and fluorouracil, leucovorin, and oxaliplatin) or gemcitabine with albumin-bound paclitaxel have the potential to improve overall survival for patients with advanced disease. Alternative approaches to incorporate immunotherapy have shown more promise such as use of immune checkpoint inhibitors for selected patients in the maintenance setting and potential vaccine therapies in the postsurgery adjuvant setting. It is vital to perform molecular profiling in all patients with PDAC to identify potential treatment targets, and to enroll patients in clinical trials whenever possible.
Review • Journal • BRCA Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)
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KRAS mutation
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gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • irinotecan • leucovorin calcium
22d
Germline Variant Spectrum in Southern Italian High-Risk Hereditary Breast Cancer Patients: Insights from Multi-Gene Panel Testing. (PubMed, Curr Issues Mol Biol)
Variants of uncertain significance were detected in 20% of patients, emphasizing the ongoing challenge of variant interpretation in the era of multi-gene panel testing. These findings not only enhance our understanding of the genetic landscape of breast cancer in Southern Italy but also provide a foundation for developing more targeted, population-specific approaches to genetic testing and counseling, ultimately contributing to the advancement of precision medicine in oncology.
Journal • BRCA Biomarker
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TP53 (Tumor protein P53) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C)
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RAD51C mutation
23d
The strand exchange domain of tumor suppressor PALB2 is intrinsically disordered and promotes oligomerization-dependent DNA compaction. (PubMed, iScience)
Intrinsically disordered DBDs are prevalent in the human proteome. PALB2-DBD and similar IDRs may use a chaperone-like mechanism to aid formation and resolution of DNA and RNA multichain intermediates during DNA replication, repair and recombination.
Journal
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51 (RAD51 Homolog A)
25d
Elucidating acquired PARP inhibitor resistance in advanced prostate cancer. (PubMed, Cancer Cell)
For BRCA2 HomDels, selection for rare subclones without BRCA2-HomDel is observed following PARPi, confirmed by single circulating-tumor-cell genomics, biopsy fluorescence in situ hybridization (FISH), and RNAish. These data support the need for restored HRR function in PARPi resistance.
Journal • BRCA Biomarker • PARP Biomarker • Metastases
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BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset)
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PALB2 mutation • BRCA mutation
26d
Survival Outcomes and Genetic Characteristics of Resected Pancreatic Acinar Cell Carcinoma. (PubMed, Ann Surg Oncol)
Resection of pACC is associated with favorable survival outcomes, even in the setting of oligometastatic disease. Mutations in the HRR pathway are common, providing opportunities for potential targeted therapeutic options.
Journal • Tumor mutational burden • BRCA Biomarker
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TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2)
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TMB-H • PALB2 mutation
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5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium
27d
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
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HRD • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • BARD1 mutation
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FoundationOne® CDx • OncoGuide™ NCC Oncopanel System
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gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • irinotecan • leucovorin calcium
1m
Secondary findings in 443 exome sequencing data. (PubMed, Ann Hum Genet)
Thirteen of above mentioned variants were classified as known pathogenic and four as expected pathogenic. The information collected in our study may lead to the prevention of severe morbidity and mortality and provides additional insight into the genetic background of the Serbian population.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • PALB2 (Partner and localizer of BRCA2) • MSH2 (MutS Homolog 2) • MYH7 (Myosin Heavy Chain 7)
1m
Homologous recombination (HR) and DNA damage repair (DDR) somatic alterations in metastatic colorectal cancer (mCRC): results from the comprehensive genomic profiling (CGP) trial FPG500 (AIOM 2024)
Background : Treatment (tx) of MSS/MMRp mCRC relies mainly on oxaliplatin (oxa)- or irinotecan-based doublet chemotherapy regimens, with no biomarker reported so far, allowing the selection of one tx over the other. HR-DDRa is associated with MSI-H or TMB-H. Pts with MSS HR-DDRa tumors benefit from oxa-based first line treatment. Longer FU, allowing mature OS data, and wider cohorts are warranted.
Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • Metastases
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TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCL (FA Complementation Group L) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
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TMB-H • MSI-H/dMMR
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TruSight Oncology 500 Assay
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oxaliplatin • irinotecan
1m
Germline pathogenic variants in prostate cancer. (PubMed, Pathol Res Pract)
Individuals with a family history of cancer were significantly more likely to have a pathogenic or likely pathogenic variant than those without one (p = 0.002). Overall, our results show the necessity for future research with a larger sample size to better explain the relationship between clinicopathologic data and genetic variants.
Journal • BRCA Biomarker
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TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MUTYH (MutY homolog) • HOXB13 (Homeobox B13) • LZTR1 (Leucine Zipper Like Transcription Regulator 1)
1m
Pathogenic variants in cancer susceptibility genes predispose to Ductal Carcinoma In situ of the breast. (PubMed, Clin Cancer Res)
The enrichment of PVs in ATM, BRCA1, BRCA2, CHEK2 and PALB2 among women with DCIS suggests that multigene panel testing may be appropriate for women with DCIS. Elevated risks of contralateral breast cancer in carriers of PVs in high penetrance genes with DCIS confirmed the utility of testing for surgical decision-making.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
1m
Splicing Dysregulation of Non-Canonical GC-5' Splice Sites of Breast Cancer Susceptibility Genes ATM and PALB2. (PubMed, Cancers (Basel))
The mapping of SRE-rich intervals in minigenes is a valuable approach for the identification of spliceogenic variants that outperforms any prediction software. Indeed, 12 spliceogenic SRE-variants were identified in the critical intervals.
Journal
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ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • SRSF2 (Serine and arginine rich splicing factor 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)
1m
BRCA2 and TP53 Mutations in a Breast Cancer Patient: A Case Report and Review of the Literature. (PubMed, Cureus)
Multigene tests are essential in the treatment approach to young BC patients, since the detection of specific mutations may help guide changes in preventive measures and treatment plans. This report describes a rare case of BC in a young patient with pathogenic germline variants in BRCA2 and TP53 genes and also presents a literature review of the topic.
Review • Journal • BRCA Biomarker
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
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TP53 mutation • BRCA2 mutation + TP53 mutation
1m
Evaluation of a Spike-in Method to Detect CNV Events Using Next-Generation Sequencing (NGS) Short-Read Technology (AMP 2024)
We demonstrate the utility of an NGS standardization spike-in control to accurately detect large CNVs and exon level duplications greater than 2 exons. This approach reduces the minimum sequencing coverage required to appropriately measure these types of alterations, thus reducing the overall cost of sequencing. Additional work to increase sensitivity and lower IS input level will be discussed.
Next-generation sequencing • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)
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TruSight Hereditary Cancer Panel
1m
The Use of Internal Controls in Next-Generation Sequencing to Improve BRCA1 and BRCA2 Gene Copy Loss Detection (AMP 2024)
SNAQ-SEQ copy loss detection was based on estimating the exon abundance of ATM, BRCA1, BRCA2, and PALB2 genes, converting abundance into copies per cell and then detecting genes with significantly lower copy number. The CNV detection comparison between OCAv3 with and without SNAQ indicated that analysis with SNAQ was more robust, giving a result for every gene in every sample. Further, there were copy losses detected by OCAv3 that were not supported by SNAQ analysis.
Next-generation sequencing • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)
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Oncomine™ Comprehensive Assay v3M
1m
Oncologic outcomes of incidental serous tubal intraepithelial carcinoma and associated high-grade serous carcinoma in high-risk patients undergoing risk-reducing surgery. (PubMed, Int J Gynecol Cancer)
The study supports the critical need for timely risk-reducing surgery in high-risk populations, as well as a comprehensive pathologic examination along with vigilant post-operative surveillance. Consensus guidelines for management of serous tubal intraepithelial carcinoma are necessary to identify a group of patients at higher risk of progression to primary peritoneal carcinoma and optimize patient care.
Journal • Surgery
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
2ms
Prevalence of BRCA1, BRCA2, and PALB2 genomic alterations among 924 Taiwanese breast cancer assays with tumor-only targeted sequencing: extended data analysis from the VGH-TAYLOR study (SABCS 2024)
This study reported a cohort of Taiwanese breast cancers harboring mutations in BRCA1, BRCA2, and PALB2 through tumor-only sequencing, which underscores the impact of these genes on breast cancer risk and potential therapeutic opportunities. Tumor-only sequencing has enabled a greater number of patients to uncover their genomic alterations, offering additional insights for management strategies. These include recommendations for germline testing and the prospective utilization of PARP inhibitors to augment treatment efficacy.
BRCA Biomarker • PARP Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A)
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BRCA2 mutation • BRCA1 mutation • PALB2 mutation • BRCA mutation • RAD51 mutation
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Oncomine™ Comprehensive Assay v3M
2ms
Serial circulating tumor DNA (ctDNA) assessment to predict treatment response and identify genomic evolution in patients with metastatic breast cancer (mBC). (SABCS 2024)
Decrease in TF, but not maxVAF, at 1-2 weeks after starting next therapy is correlated with clinical response at time of restaging and can provide an early assessment of treatment response. Genomic evolution with both emerging and disappearing alterations, including in genes clinically actionable in breast cancer as well as genes likely associated with CH, was frequently identified by serial liquid biopsies, both at time of progression and while on treatment.
Clinical • BRCA Biomarker • Circulating tumor DNA • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • DNMT3A (DNA methyltransferase 1) • PALB2 (Partner and localizer of BRCA2)
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TP53 mutation • PIK3CA mutation • ATM mutation • PTEN mutation • PALB2 mutation
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FoundationOne® Liquid CDx
2ms
Genomic and transcriptomic analyses of residual invasive triple-neg breast cancer after neoadjuvant chemotherapy in prospective MIRINAE trial (a randomized phase II trial of adjuvant atezolizumab + capecitabine versus capecitabine; KCSG-BR18-21). (SABCS 2024)
TIL-high tumors were associated with immune-enriched cancer including BLIA and TME subtypes. Ongoing analysis of invasive disease-free survival as the primary endpoint in each arm of MIRINAE trial and the role of atezolizumab in association with genomic features will provide deeper insights into the role of ICIs as adjuvant therapy.
Clinical • P2 data • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • HRD (Homologous Recombination Deficiency) • CD8 (cluster of differentiation 8) • PALB2 (Partner and localizer of BRCA2) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • CD4 (CD4 Molecule) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • IRF4 (Interferon regulatory factor 4) • CD3D (CD3d Molecule) • GZMK (Granzyme K) • NDRG1 (N-Myc Downstream Regulated 1)
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TP53 mutation • BRCA1 mutation • PIK3CA mutation • PALB2 mutation • PIK3R1 mutation
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FoundationOne® CDx • Prosigna™ Breast Cancer Prognostic Gene Signature Assay
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Tecentriq (atezolizumab) • capecitabine
2ms
Title: Case report of Breast cancer in a transgender PALB2 pathogenic variant carrier taking hormone therapy (SABCS 2024)
The patient received 4 cycles of dose dense Adriamycin Cytoxan (AC) as neoadjuvant therapy followed by right breast skin sparing mastectomy with sentinel node biopsy...Patient completed adjuvant postmastectomy radiation 5000 cGy in 25 fractions and started tamoxifen... Despite a growing population of gender aware patients, research is limited on genetic counseling for those individuals with a hereditary cancer predisposition syndrome. Clinical guidelines have been developed and adopted for this population in terms of management, but predictive testing for hereditary cancer syndromes is not the standard of care. Our recommendation is that individuals considering gender reassignment surgery and hormonal therapies consider multigene hereditary cancer panel testing to further stratify their risk for cancer prior to initiation.
Clinical • BRCA Biomarker • Case report
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ER (Estrogen receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)
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ER positive • HER-2 negative
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CancerNext-Expanded®
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tamoxifen • doxorubicin hydrochloride • cyclophosphamide
2ms
Clinical Outcomes and the 21-Gene Recurrence Score Assay in Early-Stage Breast Cancer Associated with CHEK2, ATM and PALB2 Germline Pathogenic Variants (SABCS 2024)
Our data demonstrate that higher Oncotype RS, CHEK2 mutations, lymphatic and vascular invasion, and higher Ki67 levels were identified as predictors of poorer RFS. Conversely, older age (>50 years), adjuvant ET, and adjuvant XRT were associated with improved RFS. Importantly, the presence of ATM, CHEK2, or PALB2 mutations did not significantly impact OS.
Clinical • Clinical data
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
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ER positive • HR positive • HER-2 negative • ATM mutation • PALB2 mutation • CHEK2 mutation • HR positive + HER-2 negative • PGR negative • HER-2 negative + ER positive
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Oncotype DX Breast Recurrence Score®Test
2ms
Prevalence of actionable genomic alterations (GA) and predictive value of tumor mutational burden (TMB) for immune checkpoint inhibitor (ICI) effectiveness in HR(+)HER2(-) metastatic breast cancer (MBC) (SABCS 2024)
Background: Pembrolizumab, an anti-PD1 antibody ICI is an FDA-approved option for patients with HR(+)HER2(-) MBC who have exhausted standard of care options and have high TMB (≥10 mut/mb, FoundationOne®CDx)... About 70% of TBx harbor at least one GA with established clinical utility. Pts with TMB10+ vs. TMB<10 had more favorable PFS and rwOS on ICI.
Checkpoint inhibition • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PALB2 (Partner and localizer of BRCA2) • NTRK (Neurotrophic receptor tyrosine kinase)
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BRCA2 mutation • BRCA1 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • HRD • PALB2 mutation • HRD + BRCA1 mutation • AKT1 mutation • HRD signature • BRCA1 fusion
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FoundationOne® CDx
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Keytruda (pembrolizumab)
2ms
PARP Inhibitors in Pancreatic Cancer with Homologous Recombination Repair Gene Mutations: A Single-Institution Experience. (PubMed, Cancers (Basel))
PARP inhibitors may be considered for patients with advanced pancreatic cancer harboring pathogenic alterations of BRCA who cannot tolerate standard chemotherapy. Maintenance PARPis can be considered in selected patients with non-BRCA/non-PALB2 HRR mutations.
Journal • BRCA Biomarker • PARP Biomarker
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HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset)
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PALB2 mutation • PARP1 mutation
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Lynparza (olaparib)
2ms
Implementing the Risk Stratification and Clinical Management of Breast Cancer Families Using Polygenic Risk Score Evaluation: A Pilot Study. (PubMed, J Pers Med)
This study showed that in BC families, the PRS might help to quantify the weight of the genetic familial background, improving the individual risk stratification and contributing to personalized clinical management for carrier and non-carrier women.
Journal
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)
2ms
PALB2 analysis in the diagnostic process of breast cancer: An Italian monocentric experience. (PubMed, Tumori)
Pedigree analysis revealed a family history of breast and ovarian cancer syndrome in all PALB2 pathogenic variants carriers (early breast cancer onset, bilateral breast cancer and ovarian cancer). In conclusion, the germline analysis of BRCA1, BRCA2 and PALB2 should be included in breast cancer clinical practice as a not negligible number of PALB2 carriers could be identified and referred to specific surveillance protocols.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset)
2ms
Using AI-predicted protein structures as a reference to predict loss-of-function activity in tumor suppressor breast cancer genes. (PubMed, Comput Struct Biotechnol J)
The study also highlights the predictive performance of AlphaMissense as the premier in silico missense prediction method to predict LOF activity from missense variants in these four tumor suppressor breast cancer genes. The code for this study can be downloaded for free on GitHub (https://github.com/rohandavidg/CarePred).
Journal
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51C (RAD51 paralog C)
2ms
Quantitative Assessment of PALB2 and BRIP1 Genes Expression in the Breast Cancer Cell Line under the Influence of Tamoxifen. (PubMed, Galen Med J)
Our findings showed a significant alteration between PALB2 gene expression in the TAM-treated breast cancer cell line and the control cell line. The quantitative assessment of mentioned genes as possible markers could be considered a non-invasive method for breast cancer in the processes of prognostic evaluations, screening, and treatment monitoring.
Preclinical • Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)
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tamoxifen
2ms
Phenotypic evaluation of deep learning models for classifying germline variant pathogenicity. (PubMed, NPJ Precis Oncol)
Model predictions for missense variants in BRCA1, BRCA2 and PALB2, but not ATM and CHEK2, were associated with breast cancer risk. However, deep learning models had limited clinical utility when specifically applied to variants of uncertain significance.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
2ms
Somatic gene mutations involved in DNA damage response/Fanconi anemia signaling are tissue- and cell-type specific in human solid tumors. (PubMed, Front Med (Lausanne))
Furthermore, these gene alteration patterns significantly impact patient survival and disease-free periods. Collectively, our findings not only enhance our understanding of cancer development and progression but also have significant implications for cancer patient care and prognosis, particularly in the development of effective therapeutic strategies.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • XRCC2 (X-Ray Repair Cross Complementing 2) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • MAD2L2 (Mitotic Arrest Deficient 2 Like 2) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FAAP24 (FA Core Complex Associated Protein 24) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
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ATM mutation
2ms
Association of Gene Variant Type and Location with Breast Cancer Risk in the General Population. (PubMed, medRxiv)
Women carrying protein truncating variants in exon 11 have a lower breast cancer risk in the population-based cohorts, older age at diagnosis and higher rates of estrogen receptor negative breast cancer than women with exon 1-10 or exon 13-27 truncation variants in population-based and clinical testing cohorts. Meaning: Incorporating pathogenic variant type and location in cancer risk models may improve individualized risk prediction.
Journal
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ER (Estrogen receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
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ER negative
2ms
Molecular and Clinical Features of Pancreatic Acinar Cell Carcinoma: A Single-Institution Case Series. (PubMed, Cancers (Basel))
One patient was found to have RET fusion and responded favorably to selpercatinib for over 42 months...One of the additional two cases who underwent BostonGene testing was found to have NTRK1 fusion. RNA and TME analysis by Boston Gene of the two cases reported immune desert features and relatively lower RNA levels of CEACAM5, CD47, CD74, and MMP1 and higher RNA levels of CDH6 compared with PDAC.
Journal • BRCA Biomarker
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KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CD74 (CD74 Molecule) • PALB2 (Partner and localizer of BRCA2) • CEACAM5 (CEA Cell Adhesion Molecule 5) • CDH6 (Cadherin 6) • MMP1 (Matrix metallopeptidase 1)
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BRCA2 mutation • BRCA1 mutation • NTRK1 fusion • RET fusion • ATM mutation • PALB2 mutation • KRAS wild-type
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Retevmo (selpercatinib)
2ms
Prevalence Estimation of the PALB2 Germline Variant in East Asians and Koreans through Population Database Analysis. (PubMed, Cancers (Basel))
This study is the first comprehensive investigation of PALB2 variant prevalence in East Asians and Koreans using gnomAD and Korean genome databases. These findings provide essential reference data for future research and highlight the importance of region-specific genetic studies that will inform genetic counseling and hereditary cancer risk management.
Journal
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PALB2 (Partner and localizer of BRCA2)