ArticleCell discovery2023
Comprehensive genomic profiling of breast cancers characterizes germline-somatic mutation interactions mediating therapeutic vulnerabilities.
Article in Cell discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Somatic mutations in Middle East and North Africa breast cancer patients: a systematic review.The oncologist · 2025Pooled it
- Sitravatinib plus tislelizumab in locally recurrent or metastatic triple-negative breast cancer: a multi-cohort, single-arm, phase II clinical trial (SPARK Trial).Molecular cancer · 2025Trial
- Capivasertib plus fulvestrant in patients with HR-positive/HER2-negative advanced breast cancer: phase 3 CAPItello-291 study extended Chinese cohort.Nature communications · 2025Trial
- Molecular cartography of breast cancer: decoding genomes, heterogeneity and the tumor microenvironment for personalized targeted therapeutics.Molecular biology reports · 2026Review
- Marine-Derived Fungal Metabolite MHO7 Promotes Breast Cancer Apoptosis as a Hippo Pathway Regulator by Modulating the YAP-TEAD Axis.Marine drugs · 2026Article
- Landscape of somatic genetic alterations and PAM50 intrinsic subtypes in breast cancer associated with germline pathogenic variants in DNA-repair genes.Journal of the National Cancer Institute · 2026Article
- Testican-1 activates Wnt/β-Catenin signaling to drive colorectal cancer progression.Oncogenesis · 2026Article
- Age-related genomic characterization and therapeutic targets in Chinese breast cancer: insights from prospective targeted sequencing and clinical data analysis.BMC medicine · 2026Article
- Article
- Tumor ecosystem subtyping of breast cancer based on somatic mutations and network propagation reveals distinct prognostic and genomic landscapes.Frontiers in genetics · 2026Article
- Pathogenic variants in affected and unaffected individuals from Indonesian familial cancer: a multigene panel analysis.Scientific reports · 2025Article
- Engineered crRNA Drives RPA-T7-CRISPR/Cas14a Cascade for Ultrasensitive Detection of ctDNA PIK3CA H1047R.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- A review of the use of tumour DNA methylation for breast cancer subtyping and prediction of outcomes.Clinical epigenetics · 2025Review
- Precision treatment in breast cancer: Leveraging genetic interactions.Clinical and translational medicine · 2025Article
- Genomic spectra of lymphovascular invasion in breast cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- Comprehensive germline and somatic profiling of high-risk Thai breast cancer via next-generation sequencing.Scientific reports · 2025Article
- Somatic and germline aberrations in homologous recombination repair genes among Chinese high-risk breast cancer patients by multi-gene next-generation sequencing.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Phytochemicals in Breast Cancer Prevention and Treatment: A Comprehensive Review.Current issues in molecular biology · 2025Review
- A Review on Integrating Breast Cancer Clinical Data: A Unified Platform Perspective.Current treatment options in oncology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Germline-somatic mutation interactions are universal and associated with tumorigenesis, but their role in breast cancer, especially in non-Caucasians, remains poorly characterized. We performed large-scale prospective targeted sequencing of matched tumor-blood samples from 4079 Chinese females, coupled with detailed clinical annotation, to map interactions between germline and somatic alterations. We discovered 368 pathogenic germline variants and identified 5 breast cancer DNA repair-associated genes (BCDGs; BRCA1/BRCA2/CHEK2/PALB2/TP53). BCDG mutation carriers, especially those with two-hit inactivation, demonstrated younger onset, higher tumor mutation burden, and greater clinical benefits from platinum drugs, PARP inhibitors, and immune checkpoint inhibitors. Furthermore, we leveraged a multiomics cohort to reveal that clinical benefits derived from two-hit events are associated with increased genome instability and an immune-activated tumor microenvironment. We also established an ethnicity-specific tool to predict BCDG mutation and two-hit status for genetic evaluation and therapeutic decisions. Overall, this study leveraged the large sequencing cohort of Chinese breast cancers, optimizing genomics-guided selection of DNA damaging-targeted therapy and immunotherapy within a broader population.
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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.