Characterization of the genomic landscape and actionable mutations in Chinese breast cancers by clinical sequencing

Abstract

The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that NF2 loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer.

Normal tissue adjacent to tumor expression profile analysis developed and validated a prognostic model based on Hippo‐related genes in hepatocellular carcinoma

“…NF2 mutations have been observed in many tumors, which encode Merlin proteins that cannot inhibit tumorigenesis. [37][38][39] The loss-of-function of NF2 severely compromises Hippo signaling activity through the major effector YAP, resulting in hepatomegaly and liver cancers. 40 To date, there have been no reports on the use of NF2 as a prognostic factor in cancer.…”

Characterization of Frequently Mutated Cancer Genes and Tumor Mutation Burden in Chinese Breast Cancer

“…According to molecular subtype, breast cancer is divided into Luminal A, Luminal B, HER2-enriched, and triple-negative subtypes, among which the luminal subtype, accounting for 65% to 70% of the cases, has the highest proportion (3). In recent years, next-generation sequencing (NGS) has accelerated the systematic characterization of the genomic landscape of breast cancer, which contributed to our current understanding of the unique and shared genomic features of the four breast cancer molecular subtypes (4)(5)(6)(7). Genomic aberrations in a number of genes, including TP53 and PIK3CA, have been implicated in the development of breast cancer (7).…”

“…In recent years, next-generation sequencing (NGS) has accelerated the systematic characterization of the genomic landscape of breast cancer, which contributed to our current understanding of the unique and shared genomic features of the four breast cancer molecular subtypes (4)(5)(6)(7). Genomic aberrations in a number of genes, including TP53 and PIK3CA, have been implicated in the development of breast cancer (7). While genomic studies of breast cancer are mainly performed in patients from Western countries (5,8,9), the increasing efforts in investigating the features of Chinese patients with breast cancer have revealed their unique epidemiological characteristics.…”

Identification of Fanconi Anemia Pathway Genes as Novel Prognostic Biomarkers and Therapeutic Targets for Breast Cancer

“…Moreover, compensatory mutations in BRCA1 and BRCA2 that restore homologous recombination (HR) functionality in initially cisplatin sensitive tumors is able to develop cisplatin resistance [33]. Comprehensively revealing mutation characteristics in breast cancer elucidates on the mutational diversity among different molecular subtypes, enables the identi cation of potential treatment biomarkers, and provides a basis for genomic targeting strategies and clinical trials [34]. Given the signi cant differential expression of genes in the FA pathway, we further explored their molecular characteristics.…”