Department of Digestive Surgery, Hôpital Saint-Antoine AP-HP, University Pierre et Marie Curie Paris VI, 184 rue du Faubourg Saint-Antoine, 75571 Paris, France.
Fam Cancer. 2010 Dec;9(4):589-94. doi: 10.1007/s10689-010-9367-0.
MYH associated polyposis is a hereditary syndrome responsible for early colorectal cancer with a distinct genetic pathway from the Familial Adenomatous Polyposis or the Hereditary Non Polyposis Colorectal Cancer syndrome. We have studied a family with three members bearing a biallelic mutation in MYH at c.1185_1186dup. One patient who developed colon cancer had loss of expression of MLH1 on tumoral tissue and microsatellite instability (MSI) phenotype. Analysis of MLH1 based on his blood sample revealed no germline mutation or large genomic deletion. No methylation of the promoter was identified in tumoral DNA. No transversion mutations were identified in APC or KRAS in tumor DNA of this patient. Loss of expression of MLH1 was due to a transversion in intron 7 at position +5 (c.588 + 5G > T) leading to a complete deletion of exon 7 at the RNA level. This observation demonstrates that MLH1 can be a target of MYH transversions leading to MSI phenotype.
MYH 相关息肉病是一种遗传性综合征，可导致结直肠癌，其遗传途径与家族性腺瘤性息肉病或遗传性非息肉病性结直肠癌综合征不同。我们研究了一个家族，该家族的三名成员在 c.1185_1186dup 处存在 MYH 的双等位基因突变。一位发生结肠癌的患者肿瘤组织中 MLH1 的表达缺失且存在微卫星不稳定（MSI）表型。对其血液样本进行的 MLH1 分析未发现胚系突变或大片段基因缺失。肿瘤 DNA 中未发现启动子甲基化。该患者肿瘤 DNA 中 APC 或 KRAS 未发生转换突变。MLH1 的表达缺失是由于 7 号内含子位置 +5（c.588 + 5G > T）的颠换，导致 RNA 水平上 7 号外显子完全缺失。这一观察结果表明，MLH1 可能是 MYH 颠换的靶点，导致 MSI 表型。
