A rare MSH2 mutation causes defective binding to hMSH6, normal hMSH2 staining, and loss of hMSH6 at advanced cancer stage

作者：Loconte Daria Carmela; Patruno Margherita; Lastella Patrizia; Di Gregorio Carmela; Grossi Valentina; Forte Giovanna; Ingravallo Giuseppe; Varvara Dora; Bagnulo Rosanna; Simone Cristiano; Resta Nicoletta; Stella Alessandro^*

来源：Human Pathology, 2014, 45(10): 2162-2167.

DOI：10.1016/j.humpath.2014.05.019

• Lynch syndrome
• Mismatch repair
• MSH2
• MSH6
• Second hit
• Variants of unknown significance

Lynch syndrome is caused by germline mutations in 1 of the 4 DNA mismatch repair genes (MLH1, MSH2, A1SH6, and PMS2). Mutations in MSH2 cause concomitant loss of hMSH6, whereas MLR I mutations lead to concurrent loss of PMS2. Much less frequent mutations in MSH6 or PMS2 are associated with the isolated loss of the corresponding proteins. We here demonstrate the causative role of the first germline mutation of MSH2, c.1249-1251 dupGTT (p.417 V-4181 dupV), associated with normal hMSH2 expression and lack of hMSH6 protein despite a normal MSH6 gene sequence. hMSH6 protein was completely lost only in advanced cancer stage

• 出版日期2014-10