Novel germline CDK4 mutations in patients with head and neck cancer

Abstract

BackgroundCyclin-dependent kinase 4 (CDK4) together with its regulatory subunit cyclin D1, governs cell cycle progression through G1 phase. Cyclin-dependent kinase inhibitors, including p16INK4A in turn regulate CDK4. In particular, deregulation of the p16/CDK4/cyclin D1 complex has been established in a variety of human tumors including gliomas, sarcomas, melanoma, breast and colorectal cancer. However, changes in CDK4 have rarely been observed.MethodIn this study we used a combination of PCR-SSCP and direct sequencing for mutational screening of CDK4. DNA was isolated from peripheral blood leukocyte of patients with squamous cell carcinoma of head and neck, for screening germline mutations in coding regions of CDK4.ResultsVariations observed in exon 2 and 5 were three missense mutations, g5051G > C (Ser52Thr), g5095G > C (Glu67Gln), g5906C > A, g5907C > G (Pro194Ser) and novel frame shift mutations g7321_23delTGA, g7121_7122insG, g7143delG in exon 7 and 3′UTR respectively.ConclusionIn conclusion, two novel mutations were found in N terminal domain which indicates that CDK4 mutation may play a major role in the development and progression of squamous cell carcinoma of head and neck.

A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis

“…Mutations in exon 2 of CDK4 have been related to hereditary melanoma (Bressac-de-Paillerets et al., 2002; Goldstein et al., 2006; Wölfel et al., 1995). Recently, two novel mutations in the N-terminal domain of CDK4 were related to head and neck cancer (Sabir et al., 2012). CDK4 has also been characterized as an essential component for c-neu/ERBB-2 -induced breast cancer (Landis et al., 2006).…”

Genetic Polymorphisms of XPC, XPD, XPG Genes and their Association with Radiotherapy Induced Toxicity among Head and Neck Cancer Patients: A Hospital Based Study from Maharashtra

“…stress and DNA repair pathways [2]. The commonly followed treatment of locoregionally advanced HNC is surgery followed by adjuvant radiation therapy or concurrent chemo-radiation [3,4].…”

“…Tobacco and alcohol habits are dominant risk factors responsible for HNC along with other environmental carcinogens. Genetic susceptibility of an individual towards carcinogenesis depends on genetic variants of genomic determinants such as genes involved in cell cycle regulation, carcinogen detoxification, oxidative stress and DNA repair pathways [ 2 ]. The commonly followed treatment of locoregionally advanced HNC is surgery followed by adjuvant radiation therapy or concurrent chemo-radiation [ 3 , 4 ].…”

The genetic variants of LINC-PINT are related to head and neck squamous cell carcinoma susceptibility in Chinese population

“…This is also one of the main research directions to improve the survival rate of head and neck tumors in the future (Langer, 2012;Yoshizaki, Ito et al, 2012). Although the speci c pathogenesis of HNSCC is still unclear, previous studies have con rmed that risk factors including smoking, drinking, virus infection, environmental factors, and genetic factors exhibit a vital role in the pathogenesis of HNSCC (Akhtar, Sheikh et al, 2012;Sabir, Baig et al, 2012;Smith, Rubenstein et al, 2012). However, many people are exposed to these risk factors, but a very small number of people will suffer from HNSCC (Sturgis and Wei, 2002).…”