ArticleOncogene2017
Compromised BRCA1-PALB2 interaction is associated with breast cancer risk.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
58 citing papers in PubMed, 89 citations in OpenAlex.
- A phase II study of talazoparib monotherapy in patients with wild-type BRCA1 and BRCA2 with a mutation in other homologous recombination genes.Nature cancer · 2022Trial
- Germline RBBP8 variants associated with early-onset breast cancer compromise replication fork stability.The Journal of clinical investigation · 2020Trial
- Multidimensional molecular mechanisms of drug resistance in breast cancer: Implications for clinical decision‑making and treatment strategies (Review).Oncology reports · 2026Review
- Histomorphological and Molecular Features of Colonic Large-Cell Neuroendocrine Carcinoma in a Patient With Familial Adenomatous Polyposis: A Case Report and Review of Literature.International journal of surgical pathology · 2026Review
- Site-saturation functional screens identify PALB2 missense variants associated with increased breast cancer risk.Nature communications · 2026Article
- Potential role of Fanconi anemia pathway in the pathogenesis of endometrial cancer (Review).Molecular medicine reports · 2025Review
- Breast cancer gene-1 (BRCA1) potentiates maladaptive repair after kidney injury.The Journal of experimental medicine · 2025Article
- Association between single nucleotide polymorphisms of DNA repair genes (BRCA1, BRCA2, and PALB2) and breast cancer incidence in a subset of Iranian population.Hereditary cancer in clinical practice · 2025Article
- Structural analysis of genetic variants of the human tumor suppressor PALB2 coiled-coil domain.Bioscience reports · 2025Article
- Hodgkin lymphoma and Ewing sarcoma in pediatric patient carrying germlineFrontiers in oncology · 2025Article
- Proline variants in the BRCA1 coiled-coil domain disrupt folding and binding to PALB2.Protein science : a publication of the Protein Society · 2025Article
- Installation of an Indole on the BRCA1 Disordered Domain Using Triazine Chemistry.Biomolecules · 2024Article
- PALB2 germline mutations in a large cohort of Middle Eastern breast-ovarian cancer patients.Scientific reports · 2023Article
- Refinement of the assignment to the ACMG/AMP BS3 and PS3 criteria of eightFrontiers in oncology · 2023Article
- Impact of DNA damage repair alterations on prostate cancer progression and metastasis.Frontiers in oncology · 2023Review
- Computed cancer interactome explains the effects of somatic mutations in cancers.Protein science : a publication of the Protein Society · 2022Article
- Rare germline variants in PALB2 and BRCA2 in familial and sporadic chordoma.Human mutation · 2022Article
- BRCA1-Dependent and Independent Recruitment of PALB2-BRCA2-RAD51 in the DNA Damage Response and Cancer.Cancer research · 2022Review
- Functional assessment of missense variants of uncertain significance in the cancer susceptibility gene PALB2.NPJ breast cancer · 2022Article
- Breast cancer risks associated with missense variants in breast cancer susceptibility genes.Genome medicine · 2022Article
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 3 countries.
Funding
Abstract
The major breast cancer suppressor proteins BRCA1 and BRCA2 play essential roles in homologous recombination (HR)-mediated DNA repair, which is thought to be critical for tumor suppression. The two BRCA proteins are linked by a third tumor suppressor, PALB2, in the HR pathway. While truncating mutations in these genes are generally pathogenic, interpretation of missense variants remains a challenge. To date, patient-derived missense variants that disrupt PALB2 binding have been identified in BRCA1 and BRCA2; however, there has not been sufficient evidence to prove their pathogenicity in humans, and no variants in PALB2 that disrupt either its BRCA1 or BRCA2 binding have been reported. Here we report on the identification of a novel PALB2 variant, c.104T>C (p.L35P), that segregates in a family with a strong history of breast cancer. Functional analyses showed that L35P abrogates the PALB2-BRCA1 interaction and completely disables its abilities to promote HR and confer resistance to platinum salts and PARP inhibitors. Whole-exome sequencing of a breast cancer from a c.104T>C carrier revealed a second, somatic, truncating mutation affecting PALB2, and the tumor displays hallmark genomic features of tumors with BRCA mutations and HR defects, cementing the pathogenicity of L35P. Parallel analyses of other germline variants in the PALB2 N-terminal BRCA1-binding domain identified multiple variants that affect HR function to varying degrees, suggesting their possible contribution to cancer development. Our findings establish L35P as the first pathogenic missense mutation in PALB2 and directly demonstrate the requirement of the PALB2-BRCA1 interaction for breast cancer suppression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.