Variantes patogênicas do gene PALB2 associadas a doenças oncológicas: revisão sistemática

Abstract

INTRODUCTION: The PALB2 gene, partner and localizer of BRCA2, is often associated with susceptibility to breast cancer, considered a moderate penetrance gene. First identified in 2006 as a tumor suppressor gene, PALB2 indirectly affects BRCA2 expression and loss-of-function mutations in PALB2 cause instability in the DNA homologous recombination repair pathway. PALB2 germline monoallelic mutations have been described in studies of breast, ovarian, pancreas and prostate cancer. In addition, it is also suggested that associated malignant breast neoplasms have a more aggressive phenotype. OBJECTIVE: To identify the pathogenic germline variants of the PALB2 gene most frequently associated with oncological diseases. METHODS: This is a systematic literature review of publications, worldwide, about the pathogenic variants of the PALB2 gene associated with oncological diseases, from the last 5 years (publications between 2017 and June 2022), in PubMed databases, Science Direct and Periódico Capes. Forty-eight articles were included in this review. RESULTS: A total of 129 pathogenic germline variants of the PALB2 gene were identified in the study. Of these, 111 are associated with breast cancer, 10 with male breast cancer, 10 with pancreatic cancer, 4 with ovarian cancer and 4 with prostate cancer. The c.172_175delTTGT variant, associated with breast, pancreas, ovarian and prostate cancers, was identified in 8/48 articles (16.66%), followed by c.509_510delGA, also reported in 8 studies (16.66%). related to breast and prostate cancer. The association between female and male breast cancer was identified in c.3549C>G and c.2257C>T. Three variants were related to breast and pancreatic cancer, namely c.2167_2168del, c.3256C>T and c.3113G>A. CONCLUSION: Germline mutations in the PALB2 gene provide an increased risk of developing breast, ovarian, pancreas and prostate cancer. The identification of carriers of pathogenic variants is of fundamental importance for the individualized follow-up of these individuals, in addition to allowing the design of a specific treatment.