Bashyam Murali D, Kotapalli Viswakalyan, Raman Ratheesh, Chaudhary Ajay K, Yadav Brijesh K, Gowrishankar Swarnalata, Uppin Shantveer G, Kongara Ravikanth, Sastry Regulagadda A, Vamsy Mohana, Patnaik Sujit, Rao Satish, Dsouza Shoba, Desai Devendra, Tester Ashavaid
Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
Histopathology, Apollo Hospitals, Hyderabad, India.
Mol Carcinog. 2015 Dec;54(12):1807-14. doi: 10.1002/mc.22244. Epub 2014 Nov 24.
Lynch syndrome (LS), the most common form of familial CRC predisposition that causes tumor onset at a young age, is characterized by the presence of microsatellite instability (MSI) in tumors due to germline inactivation of mismatch repair (MMR) system. Two MMR genes namely MLH1 and MSH2 account for majority of LS cases while MSH6 and PMS2 may account for a minor proportion. In order to identify MMR genes causing LS in India, we analyzed MSI and determined expression status of the four MMR genes in forty eight suspected LS patient colorectal tumor samples. Though a majority exhibited MSI, only 58% exhibited loss of MMR expression, a significantly low proportion compared to reports from other populations. PCR-DNA sequencing and MLPA-based mutation and exonic deletion/duplication screening respectively, revealed genetic lesions in samples with and without MMR gene expression. Interestingly, tumor samples with and without MMR expression exhibited significant differences with respect to histological (mucin content) and molecular (instability exhibited by mononucleotide microsatellites) features. The study has revealed for the first time a significant proportion of LS tumors not exhibiting loss of MMR expression.
林奇综合征（LS）是导致肿瘤在年轻时发病的最常见的家族性结直肠癌易患形式，其特征是由于错配修复（MMR）系统的种系失活，肿瘤中存在微卫星不稳定性（MSI）。两个MMR基因，即MLH1和MSH2，占LS病例的大多数，而MSH6和PMS2可能占较小比例。为了确定在印度导致LS的MMR基因，我们分析了48例疑似LS患者的结直肠肿瘤样本中的MSI，并确定了四个MMR基因的表达状态。虽然大多数样本表现出MSI，但只有58%表现出MMR表达缺失，与其他人群的报告相比，这一比例显著较低。PCR-DNA测序和基于MLPA的突变及外显子缺失/重复筛查分别在有和没有MMR基因表达的样本中发现了基因损伤。有趣的是，有和没有MMR表达的肿瘤样本在组织学（粘蛋白含量）和分子（单核苷酸微卫星表现出的不稳定性）特征方面存在显著差异。该研究首次揭示了相当一部分LS肿瘤未表现出MMR表达缺失。
