Germline genomic landscapes of breast cancer patients significantly predict clinical outcomes

Germline genetic variants such as BRCA1/2 could play an important role in tumorigenesis and even clinical outcomes of cancer patients. However, only a small fraction (i.e., 10%) of cancer patients whose outcomes have been shown to be associated with germline mutations of several genes (e.g., BRCA1/2, APC, TP53, PTEN and so on). We asked if genes9 mutilations in germline genomes are associated with the clinical outcome of the majority cancer patient population. To answer this question, we applied our recently developed algorithm which enables to construct predictive models using genome sequencing data to ER+ breast cancer patients (n=755). We showed that functional gene mutations in germline genomes significantly distinguished recurred and non-recurred ER+ breast cancer patients in two independent cohorts (n=200 and 295, P=1.0x10 -7 ). These results suggest that pre-existing genetic variants in germlines could determine breast tumorigenesis and tumor evolution. Further, germline genomic information could be used for developing non-invasive tests for patients9 outcomes and drug response in breast cancer, and even other cancer types and complex diseases.