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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
    1d
    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)
    |
    TMB-H • MSI-H/dMMR
    |
    TruSight Oncology 500 Assay
    |
    oxaliplatin • irinotecan
    1d
    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
    |
    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)
    3d
    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
    |
    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)
    3d
    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)
    3d
    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
    |
    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)
    |
    TP53 mutation • BRCA2 mutation + TP53 mutation
    5d
    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
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)
    |
    TruSight Hereditary Cancer Panel
    5d
    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)
    |
    Oncomine™ Comprehensive Assay v3M
    13d
    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
    |
    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)
    16d
    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)
    No abstract available
    Clinical • Clinical data
    |
    PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
    |
    Oncotype DX Breast Recurrence Score®Test
    22d
    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)
    |
    PALB2 mutation • PARP1 mutation
    |
    Lynparza (olaparib)
    24d
    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)
    24d
    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)
    28d
    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)
    28d
    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)
    |
    tamoxifen
    29d
    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
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
    1m
    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)
    |
    ATM mutation
    1m
    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
    |
    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)
    |
    ER negative
    1m
    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)
    |
    BRCA2 mutation • BRCA1 mutation • NTRK1 fusion • RET fusion • ATM mutation • PALB2 mutation • KRAS wild-type
    |
    Retevmo (selpercatinib)
    1m
    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)
    1m
    Exploratory analyses of homologous recombination repair (HRR) gene subgroups and potential associations with secondary efficacy endpoints in the HRR-deficient population of TALAPRO-2 (TP-2) (DGHO 2024)
    Introduction: TP-2 (NCT03395197) demonstrated statistically significant improvement in rPFS with 1L talazoparib (TALA) + enzalutamide (ENZA) in patients (pts) with mCRPC with and without HRR gene alterations (HRRm; prospectively determined). Broad differential efficacy benefit was evident for TALA+ENZA vs PBO+ENZA across multiple molecular subgroups and was most pronounced for the BRCA1 - PALB2 - BRCA2 axis and CDK12.
    Clinical • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset)
    |
    BRCA2 mutation
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    |
    Talzenna (talazoparib) • Xtandi (enzalutamide capsule)
    1m
    Understanding genetic variations associated with familial breast cancer. (PubMed, World J Surg Oncol)
    Familial breast cancer has been linked to several genetic diseases and mutations, according to studies. Screening for genetic disorders is recommended by National Comprehensive Cancer Network recommendations. Evaluation of breast cancer candidate variations and risk loci may improve individual risk assessment. Only high- and moderate-risk gene variations have clinical guidelines, whereas low-risk gene variants require additional investigation. With increasing use of NGS technology, more linkage with rare genes is being discovered.
    Review • Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)
    |
    ATM mutation • PALB2 mutation • CHEK2 mutation • BRIP1 mutation
    1m
    Prevalence and outcomes of germline pathogenic variants of homologous recombination repair genes in ovarian cancer. (PubMed, Cancer Sci)
    Variants were significantly associated with serous carcinoma and advanced disease, underscoring the importance of genetic testing to develop individualized EOC treatment strategies. Considering the study period (2000-2019), the limited use of bevacizumab and poly (ADP-ribose) polymerase inhibitors as maintenance therapy should be recognized.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    Avastin (bevacizumab)
    2ms
    Homologous recombination deficiency gene panel analysis results in synchronous endometrial and ovarian cancers. (PubMed, Rev Assoc Med Bras (1992))
    Pathogenic variations confirming the diagnosis of synchronous endometrial ovarian cancer with genetic alterations were identified in all but one case. ATM gene mutation emerged as the most common alteration and has a potential association with a favorable prognosis.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • 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) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54)
    |
    TP53 mutation • HRD • RAD51D mutation • BARD1 mutation • RAD54L mutation • TP53 mutation + ATM mutation
    2ms
    The Association Between Breast Cancer Predisposing Genetic Variants and Multifocal, Multicentric Breast Cancer. (PubMed, Ann Surg Oncol)
    Genetic variant carrier cancers are not more likely to be MCMF than sporadic cancers.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    2ms
    Prevalence and spectrum of germline pathogenic variants in cancer susceptibility genes among mexican patients with exocrine pancreatic cancer. (PubMed, Pancreatology)
    We identified a significant frequency of actionable germline PVs in Mexicans with PC, wherein the majority were in a broad spectrum of genes associated with the homologous recombination DNA repair mechanism. Most pancreatic cancer associated PVs were detected in non-BRCA genes, so our findings support the recommendation of multigene panel testing for genetic cancer risk assessment of Mexican individuals with PC.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)
    2ms
    What About the Others? Clinical Management of Gynecologic Cancer Risk in Patients With Moderate-Risk Hereditary Cancer Genes (ATM, BRIP1, RAD51C, RAD51D, and PALB2). (PubMed, Clin Obstet Gynecol)
    The associated cancer risks with moderate-penetrance genes are rapidly evolving and present variable risks for the provider counseling the patient. In this review, we detail the cancer risk and management of patients with germline PV in the moderate-risk hereditary cancer genes ATM, BRIP1, RAD51C, RAD51D, and PALB2.
    Journal
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    ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    2ms
    Screening Familial Risk for Hereditary Breast and Ovarian Cancer. (PubMed, JAMA Netw Open)
    In this cross-sectional study, EHR-derived FHS7 identified thousands of patients with familial risk for breast cancer, indicating a substantial gap in genetic testing. However, limitations in EHR family history data suggested that other identification methods, such as direct-to-patient questionnaires, are required to fully address this gap.
    Retrospective data • 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
    Validation of the BOADICEA model for epithelial tubo-ovarian cancer risk prediction in UK Biobank. (PubMed, Br J Cancer)
    BOADICEA, implemented in CanRisk ( www.canrisk.org ), provides valid 10-year EOC risks and can facilitate clinical decision-making in EOC risk management.
    Journal
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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
    Mutation Spectrum Comparison between Benign Breast Lesion Cohort, Unselected Cancer Cohort and High-Risk Breast Cancer Cohort. (PubMed, Cancers (Basel))
    An unexpectedly high mutation rate of total 2% was found in the NC cohort but it was only 0.3% and 0.5% in the HR cohort and CC cohort, respectively. Our results show a clinical need to enhance genetic testing of unselected breast cancer patients to identify the high-risk patients.
    Journal • BRCA Biomarker
    |
    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) • CDH1 (Cadherin 1) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    TP53 mutation • PTEN mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51 mutation
    2ms
    Long-read DNA and cDNA sequencing identify cancer-predisposing deep intronic variation in tumor-suppressor genes. (PubMed, Genome Res)
    For eight of the 120 (6%) previously unsolved families, rare deep intronic variants in BRCA1, PALB2, and ATM create intronic pseudoexons that are spliced into transcripts, leading to premature truncations. These results suggest that long-read DNA and cDNA sequencing can be integrated into variant discovery, with strategies for accurately characterizing pathogenic variants.
    Journal
    |
    BRCA1 (Breast cancer 1, early onset) • PALB2 (Partner and localizer of BRCA2)
    2ms
    Genetic links between ovarian ageing, cancer risk and de novo mutation rates. (PubMed, Nature)
    Although we were unable to replicate the finding in independent samples from the deCODE study, it is consistent with the expected role of DNA damage response genes in maintaining the genetic integrity of germ cells. This study provides evidence of genetic links between age of menopause and cancer risk.
    Journal
    |
    PALB2 (Partner and localizer of BRCA2) • BCL6 (B-cell CLL/lymphoma 6)
    2ms
    Economic evaluation of extended panel analysis in cancer patients with historical NHS diagnostic germline genetic testing - A modeling study based on real-world data. (PubMed, Eur J Med Genet)
    Where existing NGS data for cancer susceptibility genes is stored to diagnostic standard in UK laboratories, this study suggests it is cost-effective to analyse, report and clinically manage patients and relatives by extended analysis to an 8-gene panel compared to the historical genetic testing.
    Journal • HEOR • Real-world evidence • BRCA Biomarker • Real-world
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C)
    |
    BRCA1 negative
    2ms
    Prevalence of germline variants in Brazilian pancreatic carcinoma patients. (PubMed, Sci Rep)
    Therefore, genetic testing should be offered to all Brazilian pancreatic cancer patients, regardless of their ancestry. Genes with limited or previously unrecognized associations with pancreatic cancer should be further investigated to clarify their role in cancer risk.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PALB2 (Partner and localizer of BRCA2) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • MRE11A (MRE11 homolog, double strand break repair nuclease) • MUTYH (MutY homolog) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCM (FA Complementation Group M) • FANCE (FA Complementation Group E) • MITF (Melanocyte Inducing Transcription Factor) • RECQL4( RecQ Like Helicase 4) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
    2ms
    Identification of novel candidate predisposing genes in familial nonmedullary thyroid carcinoma implicating DNA damage repair pathways. (PubMed, Int J Cancer)
    MAPK activation was a common event in tumor progression. This study supports that rare germline variants in DNA repair genes may be accountable for FNMTC susceptibility, with potential future utility in patients' clinical management, and reinforces the relevance of DICER1 in disease etiology.
    Journal • BRCA Biomarker
    |
    BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • PTCH1 (Patched 1) • ERCC2 (Excision repair cross-complementation group 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • FANCF (FA complementation group F) • DICER1 (Dicer 1 Ribonuclease III) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FLCN (Folliculin) • FANCD2 (FA Complementation Group D2) • BUB1B (BUB1 Mitotic Checkpoint Serine/Threonine Kinase B)
    2ms
    Bioinformatic Analysis of Genetic Ancestry and Germline Variant Correlation in Colombian Women with Triple-Negative Breast Cancer and High-Grade Serous Ovarian Cancer Using Hereditary Cancer Panel (EORTC-NCI-AACR 2024)
    This study demonstrates the utility of using a targeted gene panel for genetic ancestry estimation in clinical settings. Our approach revealed significant associations between genetic ancestry and the prevalence of specific germline variants in Colombian women with TNBC and HGSOC, highlighting the potential of this methodology to uncover novel insights in admixed populations.
    Clinical • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • FANCA (FA Complementation Group A) • BARD1 (BRCA1 Associated RING Domain 1)
    |
    TruSight Hereditary Cancer Panel
    2ms
    Clinical Impact of Constitutional Genomic Testing on Current Breast Cancer Care. (PubMed, Clin Oncol (R Coll Radiol))
    However, the lack of long-term clinical outcome data and incomplete understanding of variants, particularly for moderate-risk genes limits clinical application. In this review, we have summarized the key functions, risks, and prognosis of breast-cancer-predisposing genes listed in the National Health Service (NHS) England National Genomic Test Directory for inherited breast cancer and provide an update on current management implications including surgery, radiotherapy, systemic treatments, and post-treatment surveillance.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    TP53 mutation • BRCA1 mutation • PALB2 mutation • RAD51C mutation • RAD51D mutation • RAD51 mutation
    3ms
    Low dose TamOxifen and LifestylE changes for bReast cANcer prevention (TOLERANT study): Study protocol of a randomized phase II biomarker trial in women at increased risk for breast cancer. (PubMed, PLoS One)
    The aim of the study is to verify whether LDT increases circulating SHBG more than LI with or without ICR after 6 months. Secondary objectives include assessing HOMA-index, inflammatory markers, adiponectin/leptin ratio, quality of life (QoL), safety, toxicity, mammographic density, and changes in microbiome composition across groups. The study's innovation lies in its inclusion of diverse BC risk categories and combination of pharmaceutical and behavioral interventions, potentially enhancing intervention efficacy while balancing tamoxifen's side effects on QoL, especially menopausal symptoms.
    Clinical • Clinical protocol • P2 data • 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) • LEP (Leptin)
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    tamoxifen
    3ms
    Universal Genetic Testing for Newly Diagnosed Invasive Breast Cancer. (PubMed, JAMA Netw Open)
    In this cross-sectional universal genetic testing study of women with newly diagnosed invasive breast cancer, the prevalence of GPVs was 7.3%, with 5.3% of patients testing positive for B1B2P2. Among B1B2P2-women women, one-third were eligible for PARP inhibitors.
    Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
    3ms
    The Clinical and Genetic Landscape of Hereditary Cancer: Experience from a Single Clinical Diagnostic Laboratory. (PubMed, Cancer Genomics Proteomics)
    Comprehensive multigene genetic testing is necessary for appropriate clinical management of pathogenic variants' carriers. Additionally, the information obtained is important for determining the risk of malignancy development in family members of the examined individuals.
    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) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D)
    3ms
    The PARP1 selective inhibitor saruparib (AZD5305) elicits potent and durable antitumor activity in patient-derived BRCA1/2-associated cancer models. (PubMed, Genome Med)
    Collectively, these results show that the novel PARP1 selective inhibitor AZD5305 yields a potent antitumor response in PDX models with HRD and delays PARPi resistance alone or in combination with carboplatin or ceralasertib, which supports its use in the clinic as a new therapeutic option.
    Preclinical • Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • RAD51 (RAD51 Homolog A)
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    Lynparza (olaparib) • carboplatin • ceralasertib (AZD6738) • saruparib (AZD5305)
    3ms
    Preliminary Evaluation of Screening for Pancreatic Cancer in Patients With Inherited Genetic Risk (clinicaltrials.gov)
    P=N/A, N=200, Recruiting, Abramson Cancer Center at Penn Medicine | Trial completion date: May 2027 --> May 2028 | Trial primary completion date: May 2025 --> May 2026
    Trial completion date • Trial primary completion date
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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)
    3ms
    DNA-Damaging Therapies in Patients With Prostate Cancer and Pathogenic Alterations in Homologous Recombination Repair Genes. (PubMed, JCO Precis Oncol)
    Patients with BRCA1/2-mutated PC had significantly improved outcomes to PARPi but not platinum chemotherapy compared with those with HRR mutations without direct BRCA complex interaction.
    Retrospective data • Journal • BRCA Biomarker • PARP Biomarker
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    HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • GEN1 (GEN1 Holliday junction 5' flap endonuclease) • RAD54L2 (RAD54 Like 2)