Two novel sequence variants in MSH2 gene in a patient who underwent cancer genetic counseling for a very early-onset epithelial ovarian cancer

Early-onset or hereditary ovarian cancer is mostly associated with BRCA1 or BRCA2 mutations. Mismatch repair genes sequence alteration frequently cause colorectal cancer, and, in less extent, other tumors, such as ovarian cancer. Subjects with personal and/or family history suggestive for hereditary cancer should be addressed to cancer genetic counseling. The multistep Cancer Genetic Counseling model, adopted at our unit, is aimed to identification, definition and management of hereditary cancer syndrome, by a multidisciplinary approach. A woman with a very early onset epithelial ovarian cancer underwent to cancer genetic counseling and genetic testing. Two germ-line mutations have been identified in exon 11 of MSH2 gene: c.1706A>T (p.Glu569Val) and c.1711G>T (p.Glu571*). Both DNA alterations were novel mutations not yet described in literature. The first is a missense mutation that is to be considered an unclassified variant; the second is nonsense mutation that created a premature stop codon resulting in a truncated not functioning protein. In conclusion, the present report finds out two unpublished sequence alterations in exon 11 of the MSH2 gene, one on which can be considered causative of Lynch phenotype, and stresses the importance of the onco-genetic counselling in order to offer the most appropriate management of the cancer risk for the patients and her family members.