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GENE:

PALB2 (Partner and localizer of BRCA2)

News alerts, weekly reports and conference planners

Comprehensive germline and somatic profiling of high-risk Thai breast cancer via next-generation sequencing. (PubMed, Sci Rep)

Notably, germline carriers exhibited lower PIK3CA mutation rates than non-carriers. These findings advance our understanding of Thai breast cancer genomics and underscore the importance of ethnic diversity in cancer research, offering insights into tailored screening and therapeutic approaches.

3 days ago

Journal • Next-generation sequencing • BRCA Biomarker

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) • PALB2 (Partner and localizer of BRCA2) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • GATA3 (GATA binding protein 3)

HR positive • HER-2 negative • PIK3CA mutation

Oncomine™ Comprehensive Assay Plus

The breast tumor immune microenvironment of DNA double-strand break repair pathogenic variant carriers is enriched with tumor-associated macrophages. (PubMed, Cancer Epidemiol Biomarkers Prev)

These results support further characterization of macrophage characteristics and abundance in the breast tumor microenvironment of DSB repair-related pathogenic variant carriers.

4 days ago

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) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCM (FA Complementation Group M) • STAT1 (Signal Transducer And Activator Of Transcription 1) • RECQL (RecQ Like Helicase) • FANCC (FA Complementation Group C)

Germline variants analysis of Chinese breast cancer patients reveals numerous alterations in homologous recombination genes. (PubMed, Future Sci OA)

All three patients with the pathogenic variant (p.Lys91fs) in RAD51D were diagnosed with triple-negative breast cancer. HR-gene testing in breast cancer could help to find new suspected pathogenic variants and increase the clinical benefit of multi-gene testing for breast cancer.

5 days ago

Journal • BRCA Biomarker

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) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D)

Association between single nucleotide polymorphisms of DNA repair genes (BRCA1, BRCA2, and PALB2) and breast cancer incidence in a subset of Iranian population. (PubMed, Hered Cancer Clin Pract)

Our findings suggest no significant association between the rs386833395 polymorphism and BC risk in the Iranian Kurdish population, while rs80359550 and rs180177102 polymorphisms were strongly associated with BC. However, the study has several limitations, including its retrospective design, a relatively small sample size, and the potential lack of generalizability to other ethnic groups within Iran. Future studies involving larger cohorts and more diverse populations are needed to confirm these results.

7 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)

Off-label use of olaparib in uncommon tumor locations in patients with impaired homologous recombination genes. (PubMed, Farm Hosp)

There is limited published evidence on the use of olaparib in patients harboring pathogenic variants other than breast cancer genes, like PALB2 and ATM and conditions different than those authorized such as digestive tract, neuroendocrine and lung tumors. Further research is to assess the efficacy of olaparib in these patients.

8 days ago

Journal • BRCA Biomarker • PARP Biomarker

BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)

PALB2 mutation

Lynparza (olaparib)

HSR25-154: Treatment Patterns and Prognosis of Patients With HER2-Negative Early Breast Cancer and Germline Pathogenic Variants in BRCA1, BRCA2, ATM, CHEK2 and PALB2. (PubMed, J Natl Compr Canc Netw)

No abstract available

8 days ago

Journal • BRCA Biomarker

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) • CHEK2 (Checkpoint kinase 2)

HER-2 negative

Predicting Pathogenic Variants of Breast Cancer Using Ultrasound-Derived Machine Learning Models. (PubMed, Cancers (Basel))

This approach could reduce dependence on costly genetic testing and expedite the diagnostic process. However, further validation in larger and more diverse populations is needed.

9 days ago

Journal • BRCA Biomarker

Genomic Signature for Initial Brain Metastasis Velocity (iBMV) in Non-Small-Cell Lung Cancer Patients: The Elusive Biomarker to Predict the Development of Brain Metastases? (PubMed, Cancers (Basel))

Patients with a positive iBMV risk score were more likely to develop brain metastases. Validation of this signature could lead to a biomarker with the potential to guide treatment recommendations and surveillance schedules.

9 days ago

Journal

BRAF (B-raf proto-oncogene) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • GNAQ (G Protein Subunit Alpha Q) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • CDK4 (Cyclin-dependent kinase 4) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • TSC1 (TSC complex subunit 1) • RAD51D (RAD51 paralog D) • ARAF (A-Raf Proto-Oncogene)

16d

Effects of breast size on breast reconstruction in BRCA mutation carriers and genetic high-risk patients after bilateral mastectomy. (PubMed, Breast Cancer)

The preoperative breast size of gene mutation carriers influences the postmastectomy reconstructive choice. TMG and SGAP flaps are suitable options for bilateral reconstruction of genetic susceptible patients with small breasts, while DIEP flaps are preferred in larger breast sizes. With increasing breast size an elevated risk for elective revisions after either IBR or ABR need to be considered. Women with medium-to-large breasts exhibit increased morbidity related to expansion and genetic high-risk patients may benefit from prior reduction mammoplasty.

16 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2)

PALB2 mutation • BRCA mutation

20d

Structural analysis of genetic variants of the human tumor suppressor PALB2 coiled-coil domain. (PubMed, Biosci Rep)

Our findings reveal a strong correlation between the structural impact of mutations and their efficiency in homologous recombination, suggesting that our approach can be applied to study other genetic variations in PALB2. These findings hold promise for improving genetic counseling and advancing cancer research.

20 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset)

PALB2 mutation

25d

Germline analysis of an international cohort of pediatric diffuse midline glioma patients. (PubMed, Neuro Oncol)

Our study determined the prevalence of pathogenic germline variants in pediatric DMG, and suggests a role in tumorigenesis for a subset of patients.

25 days ago

Journal • BRCA Biomarker • PARP Biomarker • IO biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • FANCE (FA Complementation Group E)

25d

Pathogenic germline variants in cancer predisposition genes in patients with multiple primary cancers in an Asian population and the role of extended panel genetic testing. (PubMed, ESMO Open)

Patients with MPC were more likely to harbour a PGV. Extended testing improved PGV detection rates, particularly for less well-known cancer predisposition genes.

25 days ago

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) • TET2 (Tet Methylcytosine Dioxygenase 2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MBD4 (Methyl-CpG Binding Domain 4, DNA Glycosylase) • BARD1 (BRCA1 Associated RING Domain 1) • DDX41 (DEAD-Box Helicase 41) • FANCL (FA Complementation Group L) • CTNNA1 (Catenin Alpha 1) • RECQL4( RecQ Like Helicase 4) • SPINK1 (Serine peptidase inhibitor, kazal type 1) • CDKN1C (Cyclin Dependent Kinase Inhibitor 1C) • TNFRSF13B (TNF Receptor Superfamily Member 13B)

28d

Reduced reproductive potential in young healthy women with hereditary breast and/or ovarian cancer syndrome. (PubMed, Commun Med (Lond))

A consistent trend for reduced reproductive potential in young, healthy women with HBOC syndrome is observed, particularly in BRCA1 P/LPV carriers. These findings need to be confirmed by larger studies including also women carrying P/LPV in other HBOC syndrome-related genes.

28 days ago

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) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D)

Breast Cancer: A Heterogeneous Pathology. Prognostic and Predictive Factors - A Narrative Review. (PubMed, Chirurgia (Bucur))

Moreover, the implementation of Molecular Tumor Boards further enhances personalized treatment strategies, contributing to improved patient outcomes and survival rates. This review underscores the significance of tailored therapeutic approaches and highlights the dynamic evolution of breast cancer in clinical practice.

1 month ago

Review • Journal • BRCA Biomarker

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) • PALB2 (Partner and localizer of BRCA2)

TP53 mutation • PIK3CA mutation • PTEN mutation • PALB2 mutation

Prosigna™ Breast Cancer Prognostic Gene Signature Assay • MammaPrint • EndoPredict® • Oncotype DX Breast Recurrence Score®Test

Prophylactic breast surgery: The role of DIEP (Deep Inferior Epigastric) (PubMed, Bull Cancer)

Despite logistical challenges, this method is favored for its durability and natural outcome. INCa and other organizations are working to improve access and information for these treatments.

1 month ago

Review • Journal • BRCA Biomarker

PTEN mutation

UK-based clinical testing programme for somatic and germline BRCA1/2, ATM and CDK12 mutations in prostate cancer: first results. (PubMed, BMJ Oncol)

BRCA2 and CDK12 somatic PVs do not appear to be mutually exclusive. BRCA1 does not appear to be a significant contributor to prostate cancer progression.

1 month ago

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) • CDK12 (Cyclin dependent kinase 12)

CDK12 mutation

Reclassification of variants of uncertain significance by race, ethnicity, and ancestry for patients at risk for breast cancer. (PubMed, Front Oncol)

This study allows for improved and more equitable genetic counseling. It may also provide more reassurance to those groups that may have a higher likelihood of VUS results.

1 month ago

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) • NF1 (Neurofibromin 1) • 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)

Hodgkin lymphoma and Ewing sarcoma in pediatric patient carrying germline PALB2 variant: a case report and literature review. (PubMed, Front Oncol)

Since the patient was exposed to chemotherapy due to lymphoma prior to the development of secondary malignancy and the variant is classified as an aberration of unknown significance, the causative role of the PALB2 variant remains uncertain. Nevertheless, the presented case may indicate the possible interplay between inherited genetic predisposition and the exposure to cytostatic drugs, which both are involved in promoting secondary cancers in pediatric patients.

1 month ago

Journal

PALB2 (Partner and localizer of BRCA2)

Response to PARP inhibitor in EGFR-tyrosine kinase inhibitor-resistant metastatic lung adenocarcinoma with germline PALB2 mutation. (PubMed, Anticancer Drugs)

We present a case of EGFR-tyrosine kinase inhibitor-resistant metastatic lung adenocarcinoma with a germline PALB2 mutation that was treated with fluzoparib (an orally administered PARPi). The treatment achieved surprising results and lasted for more than 4.5 months. Our study provided evidence that metastatic lung adenocarcinoma with germline PALB2 could benefit from PARPi, which improves patient outcomes.

1 month ago

Journal • PARP Biomarker

EGFR (Epidermal growth factor receptor) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2)

HRD • PALB2 mutation

AiRuiYi (fluzoparib)

Prevalence of Constitutional Pathogenic Variant in a Cohort of 348 Patients With Multiple Primary Cancer Addressed in Oncogenetic Consultation. (PubMed, Mol Genet Genomic Med)

Patients referred for oncogenetic testing with MPM are more likely to carry pathogenic variants in cancer predisposition genes than patients with a single primary cancer (p < 0.05), especially if the cancers are related to the same predisposition syndrome. If the cancers are unrelated, no statistical difference in comparison to the single-cancer population was observed. For these latter patients, we recommend using the specific criteria of each tumor to propose appropriate genetic testing.

1 month ago

Journal • BRCA Biomarker

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) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • EPCAM (Epithelial cell adhesion molecule) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

Breast, Colorectal, and Pancreatic Cancer Mortality With Pathogenic Variants in ATM, CHEK2, or PALB2. (PubMed, J Clin Oncol)

Patients with ATM, CHEK2, or PALB2 PVs had similar breast, colorectal, and pancreatic cancer mortality to the average genetically tested patient with their cancer type.

1 month ago

Journal • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)

HER-2 positive • HER-2 negative • PGR positive • EGFR positive

Population-based study of recurrent DNA damage response gene variants in breast cancer cases. (PubMed, Breast Cancer Res Treat)

The studied DDR gene variants were present in 9% of the unselected cases. As the presence of germline pathogenic variants can provide additional value for surgical decision-making and affect the choice of oncological treatments, the results promote the benefits of genetic testing as a part of breast cancer diagnostics.

1 month ago

Journal • BRCA Biomarker

ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein) • FANCM (FA Complementation Group M)

ER positive

PALB2 germline pathogenic variants: frequency, clinical features, and functional analysis of c.3350+5G>A variant in 3987 Korean cancer patients. (PubMed, ESMO Open)

Age at first cancer diagnosis and the presence of multiple primary organ cancers are key risk factors for suspected germline PALB2 PV. Hence, strategies are required to improve adherence to the National Comprehensive Cancer Network guidelines for cancer screening and family genetic testing among Korean patients with cancer.

1 month ago

Journal

PALB2 (Partner and localizer of BRCA2)

Causative Genes of Homologous Recombination Deficiency (HRD)-Related Breast Cancer and Specific Strategies at Present. (PubMed, Curr Oncol)

Therefore, a large-scale database, including clinical information and a long-term follow-up should be established, after which a periodical assessment is mandatory. The clinical behavior of each gene should be clarified based on a large-scale database, or, in other words, real-world data.

1 month ago

Review • Journal • BRCA Biomarker • PARP Biomarker

ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • BARD1 (BRCA1 Associated RING Domain 1)

HRD • BRCA mutation

Considerations for hereditary breast and ovarian cancer syndrome molecular diagnosis: experience from the clinical practice. (PubMed, Breast Cancer Res Treat)

Testing cancer susceptibility genes using an agnostic strategy confers a diagnostic benefit for hereditary cancer syndromes compared to phenotype-driven test, without adding complexity to the study. The analysis of healthy individuals with a family history of HBOC detects pathogenic variants in a cost-efficient percentage of cases, resulting in a good alternative strategy when the index case is unavailable.

1 month ago

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) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • 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)

Neoadjuvant chemotherapy response and genetic susceptibility in recently parous women with breast cancer. (PubMed, medRxiv)

Post-partum BC occurrence is not increased in BRCA1/2 carriers; effects of rarer susceptibility genes may differ. These important effects of parity on BC in young women and those at genetic risk warrant larger prospective studies.

1 month ago

Journal • BRCA Biomarker • IO biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)

PALB2 mutation

2ms

Molecular Profiling of Sinonasal Adenoid Cystic Carcinoma: Canonical and Noncanonical Gene Fusions and Mutation. (PubMed, Am J Surg Pathol)

Noncanonical fusions were predominantly observed in metatypical AdCCs. These findings emphasize the value of comprehensive molecular profiling in correlating morphologic characteristics, genetic landscape, and clinical behavior in AdCC.

2 months ago

Journal

PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NOTCH1 (Notch 1) • NF1 (Neurofibromin 1) • RUNX1 (RUNX Family Transcription Factor 1) • PALB2 (Partner and localizer of BRCA2) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CREBBP (CREB binding protein) • BCOR (BCL6 Corepressor) • EWSR1 (EWS RNA Binding Protein 1) • KDM6A (Lysine Demethylase 6A) • EP300 (E1A binding protein p300) • DDX41 (DEAD-Box Helicase 41) • PHF6 (PHD Finger Protein 6) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D) • NFIB (Nuclear Factor I B) • RIT1 (Ras Like Without CAAX 1) • CHD2 (Chromodomain Helicase DNA Binding Protein 2) • DNM3 (Dynamin 3) • GEN1 (GEN1 Holliday junction 5' flap endonuclease) • LZTR1 (Leucine Zipper Like Transcription Regulator 1) • MYBL1 (MYB Proto-Oncogene Like 1) • TAF1 (TATA-Box Binding Protein Associated Factor 1)

2ms

Pathogenic Germline Variants in Patients With Metaplastic Breast Cancer. (PubMed, JAMA Netw Open)

In this cohort study of patients with MpBC, a substantial proportion of clinically tested patients had a PGV in a breast cancer susceptibility gene, most commonly BRCA1. Germline testing was high yield in patients with MpBC, many of whom would be included in current germline testing eligibility criteria.

2 months ago

Retrospective data • Journal • BRCA Biomarker

2ms

Mutations in homologous recombination repair genes in patients with metastatic endometrial cancer: association with clinical characteristics and prognosis. (PubMed, J Gynecol Oncol)

Somatic HRR mutations are detected in 11.8% of metastatic EC. Compared with noncarriers, HRR mutation carriers in metastatic EC have higher proportions of endometrioid carcinoma, POLEmut, and dMMR subtypes, and unique metastatic patterns. However, the prognoses are similar regardless of HRR status.

2 months ago

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) • 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)

TP53 mutation • MSI-H/dMMR • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation

2ms

Exome sequencing identifies HELB as a novel susceptibility gene for non-mucinous, non-high-grade-serous epithelial ovarian cancer. (PubMed, Eur J Hum Genet)

The other five genes were OR2T35, HELB, MYO1A and GABRP which were associated with non-high-grade serous ovarian cancer and MIGA1 which was associated with high-grade serous ovarian cancer. Further support for the association of HELB association comes from the observation that loss-of-function variants in HELB are associated with age at natural menopause and Mendelian randomisation analysis shows an association between genetically predicted age at natural menopause and endometrioid ovarian cancer, but not high-grade serous ovarian cancer.

2 months ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MSH6 (MutS homolog 6) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • GABRP (Gamma-Aminobutyric Acid Type A Receptor Subunit Pi)

2ms

Germline Pathogenic Variants and Clinical Outcomes in Asian Patients With Breast Cancer. (PubMed, Cancer Sci)

There was no significant difference in 10-year IDFS between the non-BRCA1/2 PV carrier and noncarrier groups (aHR = 1.40; 95% CI, 0.67-2.93; p = 0.37). Asian patients with breast cancer carrying germline BRCA1/2 PV, even those with a low recurrence risk, have significantly shorter 10-year IDFS than noncarriers.

2 months ago

Clinical data • Journal • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative

2ms

Beyond failure of endocrine-based therapies in HR+/HER2 negative advanced breast cancer: what before chemotherapy? A glimpse into the future. (PubMed, Crit Rev Oncol Hematol)

Trastuzumab-deruxtecan has been proven meaningfully superior to chemotherapy either in 1st and later lines after progression to CDK4/6i in HER2-low ABC and results with other ADCs as Sacituzumab Govitecan and Datopotamab-deruxtecan are promising, but the definition of cross-resistance between these drugs sharing either antibody or payload is crucial before implementing them in a useful sequence. On the other hand, the results obtained with immune checkpoint inhibitors (ICIs) in HR+/HER2-ABC contrarily to the early setting are disappointing up to now, but investigations of ICIs in combination with other targeted drugs which may increase immune response and the search for better markers of activity are under way. Moreover the anticipation in upfront treatment of ADCs or PARPi in patients with features of putative endocrine resistance and/or of less sensitiviy to CDK4/6i and the choice of therapy in patients recurring during or soon after adjuvant CDK4/6i and olaparib represent further challenges for the future.

2 months ago

Review • Journal • BRCA Biomarker • PARP Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PALB2 (Partner and localizer of BRCA2)

HER-2 positive • HR positive • HER-2 negative • PALB2 mutation • HR positive + HER-2 negative • HER-2 negative + HR positive + BRCA mutation

Lynparza (olaparib) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Trodelvy (sacituzumab govitecan-hziy) • Datroway (datopotamab deruxtecan)

2ms

Exploring breast cancer associated-gene panel for next-generation sequencing and identifying new, pathogenic variants in breast cancer from western China. (PubMed, J Cancer)

Consequently, a high-risk gene panel has been preliminarily established for early detection/diagnosis that will contribute to earlier prevention and treatment strategies for individuals with BC, particularly those residing in developing or underdeveloped countries. The identification of novel pathogenic variants within our cohort not only expands knowledge regarding genetic diagnosis applications for BC patients but also facilitates genetic counseling services for affected individuals and their families.

2 months ago

Journal • Next-generation sequencing • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PALB2 (Partner and localizer of BRCA2) • KMT2C (Lysine Methyltransferase 2C) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • TWIST1 (Twist Family BHLH Transcription Factor 1)

2ms

The homologous recombination factors BRCA2 and PALB2 interplay with mismatch repair pathways to maintain centromere stability and cell viability. (PubMed, Cell Rep)

However, cells deficient in both BRCA2/PALB2 and MLH1 have reduced survival. These results highlight a critical balance between HR and MMR factors in preserving centromere integrity and cell viability.

2 months ago

Journal • Mismatch repair

BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • CENPA (Centromere protein A)

2ms

Adjusting for Ascertainment Bias in Meta-Analysis of Penetrance for Cancer Risk. (PubMed, Stat Med)

The overall estimated BC risk for individuals with pathogenic variants are (1) 5.77% (3.22%-9.67%) by age 50 and 26.13% (20.31%-32.94%) by age 80 for ATM; (2) 12.99% (6.48%-22.23%) by age 50, and 44.69% (34.40%-55.80%) by age 80 for PALB2. The proposed method allows meta-analyses to include studies with ascertainment bias, resulting in inclusion of more studies and thereby more accurate estimates.

2 months ago

Retrospective data • Journal

ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2)

2ms

Heterogeneity of the Treatment Effect with PARP Inhibitors in Metastatic Castration-resistant Prostate Cancer: A Living Interactive Systematic Review and Meta-analysis. (PubMed, Eur Urol)

Our LMA delivers information on the effect of PARPi therapy in relation to specific gene alterations in mCRPC via an interactive web platform. The evidence suggests the greatest PARPi benefit in patients with BRCA alterations, a strong signal of benefit in patients with PALB2 or CDK12 alterations, and no benefit in patients with ATM or CHEK2 alterations.

2 months ago

Retrospective data • Review • Journal • BRCA Biomarker • PARP Biomarker

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) • CHEK2 (Checkpoint kinase 2)

2ms

Association between DNA damage repair alterations and outcomes to 177Lu-PSMA-617 in advanced prostate cancer. (PubMed, ESMO Open)

DDR alterations were not associated with outcomes following LuPSMA. This has implications for treatment sequencing in mCRPC, particularly in patients with DDR alterations.

2 months ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • RAD51 (RAD51 Homolog A)

ATM mutation • PALB2 mutation • CDK12 mutation

Pluvicto (lutetium Lu 177 vipivotide tetraxetan)

2ms

Informatics strategies for early detection and risk mitigation in pancreatic cancer patients. (PubMed, Neoplasia)

Additionally, this review points to future directions in PC diagnostics, including next-generation imaging, molecular biomarkers, and personalized medicine, aiming to overcome current diagnostic challenges and improve survival rates. Ultimately, the review advocates the adoption of informatics and AI-driven strategies to enhance early detection, reduce morbidity, and save lives in the fight against pancreatic cancer.

2 months ago

Review • Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)

PALB2 mutation

CancerSEEK

3ms

Germline variants detected by multigene panel testing in patients with suspected hereditary breast cancer. (PubMed, Surg Today)

VUSs are frequently identified during testing and it is important to monitor these individuals because VUS evaluations can change over time.

3 months ago

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) • MLH1 (MutL homolog 1) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2)

3ms

ZNF703 promotes Triple-Negative breast cancer cell progression and in combination with STK11 predicts disease recurrence (ZS -TNBC Model). (PubMed, Gene)

ZNF703 is required for the growth, invasion, and migratory behavior of TNBC cells. Downregulation of ZNF703 increases cisplatin efficacy. This study suggests that either ZNF703 alone or in conjunction with STK11 can be utilized to predict DFS in TNBC.

3 months ago

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) • ZNF703 (Zinc Finger Protein 703)

cisplatin

3ms

Comprehensive Genetic Profile of Chinese Muscle-Invasive Bladder Cancer Cohort. (PubMed, Clin Genitourin Cancer)

Our study provided comprehensive insights into genomic alterations in a cohort of Chinese MIBC, which could provide potential clues for clinical applications.

3 months ago

Journal • Tumor mutational burden

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FGFR3 (Fibroblast growth factor receptor 3) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • KMT2D (Lysine Methyltransferase 2D) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • ERCC2 (Excision repair cross-complementation group 2) • KMT2C (Lysine Methyltransferase 2C) • MUC16 (Mucin 16, Cell Surface Associated) • TTN (Titin) • AHNAK2 (AHNAK Nucleoprotein 2) • MUC4 (Mucin 4, Cell Surface Associated) • CDC27 (Cell Division Cycle 27)

TP53 mutation • TMB-H • PALB2 mutation

3ms

Los olvidados: Non-BRCA variants associated with Hereditary breast cancer in Mexican population. (PubMed, Breast Cancer Res)

Multi-gene testing implementation improves the detection of often overlooked genes related to HBOC pathogenesis and treatment. Non-BRCA GPVs in Northern Mexico correspond to one-third of the HBOC cases, including HR and DDR pathways genes that would be misdiagnosed if not tested. HR patient carriers are potential targets of iPARP therapies. The optimal approach to cancer treatment for non-BRCA mutation carriers warrants further investigation to develop newer therapies.

3 months ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)

PALB2 mutation