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The study analyzed the germline LGR profile in 17,025 cancer patients across 22 cancer types using next-generation sequencing (NGS). The study found that ovarian cancer, renal cell carcinoma, breast cancer, glioma, and thyroid carcinoma had the highest proportion of germline LGRs. Novel LGRs were found in MSH2, FANCA, and PMS2 genes, and co-occurrences were observed between germline LGRs in MSH2 and somatic SNVs/InDels in BRCA2, KTM2B, KDM5A, CHD8, and HNF1A. Samples with pathogenic and likely pathogenic germline LGRs tended to have higher mutational burden, chromosomal instability, and microsatellite instability ratio compared to samples with pathogenic germline SNVs/InDels. The study demonstrates the prevalence of pathogenic germline LGRs beyond breast and ovarian cancer, highlighting new understanding of LGRs across multiple cancer types.
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