Sporadic endometrial adenocarcinoma with MMR deficiency due to biallelic MSH2 somatic mutations

We report t he case of a woman with an early-onset endometrial adenocarcinoma who was suspected to be affected with Lynch syndrome based on tumor dMMR phenotype (MSI associated with loss of expression of MSH2 and MSH6 proteins). After complete germline and somatic evaluations, this phenotype was eventually expl ained by twoMSH2 somatic mutations and the diagnosis of Lynch-like syndrome due to an unidentifiedMSH2 germline mutation was ruled out. Somatic mosaicism at low mutation rate was unlikely as no mutation was detected by DNA analysis from various tissue samples. Nevertheless, the three patient ’s children were tested for the two mutations and these tests were negative. Biallelic somatic mutations of one MMR gene is a mechanism of invalidation of the MMR system in sporadic cases. Clinicians have to be aware of this mechanism because of the great clinical implication for the patients and their relatives.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research