Landscape of multilocus inherited neoplasia alleles syndrome in China.

Abstract

e13027 Background: Comprehensive gene panels are able to identify patients with more than one pathogenic germline mutations. This phenomenon is known as multilocus inherited neoplasia alleles syndrome (MINAS). The frequency and phenotype of double heterozygous carriers in China are still unknown. Methods: A cohort of 12514 unrelated patients with solid tumor were screened using a validated panel. DNA damage repair-associated genes ( BRCA1, BRCA2, PALB2, ATM) and DNA mismatch repair genes ( MLH1, MSH2, MSH6, PMS2, MLH3, MSH3, PMS1) are taken focused on this study. Results: 10 (2.16%) cases harboring two pathogenic/likely pathogenic mutations were identified in 464 patients with germline variant. All patients had at least one high-risk gene mutation except for G10(LC, 73y), which carried 2 ATM variants in the same allele. All patients developed tumors associated with only one of the mutation identified until now. Among 3 patients had PMS2/MSH6 mutation, G6 & G7 did not translated into recognized Lynch Syndrome due to abnormal BRCA1/2(H-risk for BC), while G8 harboring ATM (M-risk for BC) mutation developed to CRC. All of the five patients developed to breast cancer were TNBC molecular subtype. The median ages of diagnosis for BC were similar to single variation patients (44.3 vs 42, p=0.6190). Conclusions: Two double heterozygotes did not appear to have severe or different manifestations than single heterozygote. With the growing implementation of NGS based panel testing, relevant variants in two (or more) genes will be found more frequently. [Table: see text]