Inactivation of Human MutL Homolog 1 and MutS Homolog 2 Genes in Head and Neck Squamous Cell Carcinoma Tumors and Leukoplakia Samples by Promoter Hypermethylation and Its Relation With Microsatellite Instability Phenotype

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world1 and accounts for 30% to 40% of all cancers in India.2 The major risk factors for this type of cancer are tobacco intake, both in the form of smoking and chewing, alcohol consumption, and human papillomavirus infection.HNSCC is characterized by complex, nonrandom changes in its genome and often shows different types of genomic instabilities.5,6 Previous investigators7–10 reported that a substantial fraction of HNSCC tumors exhibits instability at the simple repeat sequences (microsatellites) that are distributed throughout the genome known as microsatellite instability (MIN). In colorectal and other tumors, MIN occurs because of defects in mismatch-repair (MMR) genes, such as human mutL homolog 1 (hMLH1); human mutS homolog 1, 3, and 6 (hMSH2, hMSH3, and hMSH6); and postmeiotic segregation increased 1 and 2 (PMSI and PMS2).11–14 However, involvement of MMR genes in the development of MIN in HNSCC tumors is uncertain