Abstract PS16-30: Pms1 gene: A new risk-mutation description?
Authors: Silva-Fernandes Isabelle JoyceLima , Picanço-Albuquerque Clarissa Gondim , Claudia dos Santos Luciano Maria , Wong Deysi Viviana Tenazoa , Bezerra Maria Júlia Barbosa , Bitencourt Flavio Silveira , Oliveira Francisca Fernanda Barbosa , de Barros Silva Paulo Goberlanio , Sant´anna Rosane Oliveira , Lima Marcos Venicio Alves 
Published: February 2021

INTRODUCTION: PMS1 is part of the cluster of genes related to Mismatch repair genes (MMR) and has been used for investigation in oncogenetic panels. The MMR genes play an important role in tumor control and progression, however, the role of PMS1 in this process still poorly understood and information about its role in increasing the risk of developing a hereditary cancer predisposition syndrome (SHPC) is not completely understood.AIM: To characterize clinically and genetically cancer patients with NCCN criteria for SHPC and carriers of variants in the PMS1 gene.METHODOLOGY: A total of 368 patients suspected of having SHPC, according to the National Comprehensive Cancer Network (NCCN) criteria, were investigated using a Next-Generation Sequencing (NGS) in a panel containing 31 genes. Those that showed variation in the PMS1 gene were grouped, and the tumors were characterized in clinical and molecular aspects.RESULTS: From the 368 patients analyzed, 6.8% (25/368) patients presented Variants of Uncertain Significance (VUS) in PMS1. There was a case of Breast Cancer (BC) with a variant in PMS1, not described in ClinVar, presented in heterozygosis, probably pathogenic [Chr2:190.738,325 NM_000534: c.2578delA: p.(Arg860.Glufs*14)]. Besides, this case was associated with a family history (FH) of cancer breast cancer and melanoma. It is worth mentioning that only one patient was a man, with colorectal cancer (CRC), and his FH also was CRC in addition to stomach cancer. The only change founded was the presence of VUS NM_000534:c.1615A&gt;G:p.(Met539Val) which was identified in 32% (8/25). This VUS was the only genetic alteration observed in 20% (5/25) patients with tumors in the breast (3), thyroid (1), CRC (1), and ovary (1). One of these patients had bilateral breast cancer and thyroid tumor. The patients had their age at diagnosis ranged from 25 to 65 years, with an average of 41 years. The carriers of variants exclusively in PMS1 [40% (10/25)] had different tumors: breast (6); CRC (3); ovary (2); lymphoma (1); thyroid (1); others 32% (n = 8/25) that presented additional VUS in different genes: [ATM (2); BARD (1); CDH1 (1); CHECK2 (1); NBN (1); APC (1); POLE (1)]. Different pathogenic variants (PV) [28% (n = 7/25)] also were identified, besides the previous PMS1 VUS described. The PV was founded in ATM (1); BRCA1 (3); NF1 (1); TP53 (1); MUTYH-heterozygosis (1), and PMS1 (1) gene. A double pathogenic variation was identified in a patient (MUTYH in heterozygosis and BRCA1). The findings in PMS1, even currently classified as VUS, should highlight observation for the clinical and familiar history. Genetic panels should be increasingly used in the investigation of SPHC.CONCLUSION: The roles of PMS1 in cancer progression need further investigations. A few numbers of reports have been identified on germline PMS1 mutations, considering defined disease phenotypes. Therefore, the performance of genetic panels, including the PMS1 gene, in SHPC further investigations will expand our knowledge and permit precise genetic counseling.

Citation Format: Isabelle JoyceLima Silva-Fernandes, Clarissa Gondim Picanço-Albuquerque, Maria Claudia dos Santos Luciano, Deysi Viviana Tenazoa Wong, Maria Júlia Barbosa Bezerra, Flavio Silveira Bitencourt, Francisca Fernanda Barbosa Oliveira, Paulo Goberlanio de Barros Silva, Rosane Oliveira Sant´anna, Marcos Venicio Alves Lima. Pms1 gene: A new risk-mutation description? [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-30.