1. Mutational landscape of gingivo-buccal oral squamous cell carcinoma reveals new recurrently-mutated genes and molecular subgroups
- Author
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Partha P. Majumder, D. Sarkar, Souvik Mukherjee, S. K. Das, Arindam Maitra, Debdutta Ganguli, Sudhir Nair, D. Sutradhar, Santosini Patra, S. Sarkar, Nidhan K. Biswas, Pankaj Chaturvedi, D. Das, Maharaj K. Bhan, T. S. V. C. Rao, M. Rama-Gowtham, Kishore Amin, Analabha Basu, Rudra Sankar Dhar, Shantanu Kumar, B. Roychowdhury, Santosh Nikam, Bijan B. Bairagya, Rajiv Sarin, Anil K. D'Cruz, Tejpal Gupta, Debasmita Dutta, Neeta Sarkar-Roy, Asawari Patil, Sanchita Mahapatra, M. Nobre, Poonam Gera, Indranil Bagchi, M. H. K. Mujawar, Pradnya Kowtal, and Biman Kanti Roy
- Subjects
Adult ,Male ,General Physics and Astronomy ,Disease ,Kaplan-Meier Estimate ,Biology ,Bioinformatics ,General Biochemistry, Genetics and Molecular Biology ,Article ,Biological pathway ,medicine ,Humans ,In patient ,Basal cell ,Gene ,Exome sequencing ,Caspase 8 ,Multidisciplinary ,Cancer ,General Chemistry ,Buccal administration ,Middle Aged ,medicine.disease ,Cadherins ,stomatognathic diseases ,Mutation ,Carcinoma, Squamous Cell ,Female ,Mouth Neoplasms ,Tumor Suppressor Protein p53 - Abstract
Gingivo-buccal oral squamous cell carcinoma (OSCC-GB), an anatomical and clinical subtype of head and neck squamous cell carcinoma (HNSCC), is prevalent in regions where tobacco-chewing is common. Exome sequencing (n=50) and recurrence testing (n=60) reveals that some significantly and frequently altered genes are specific to OSCC-GB (USP9X, MLL4, ARID2, UNC13C and TRPM3), while some others are shared with HNSCC (for example, TP53, FAT1, CASP8, HRAS and NOTCH1). We also find new genes with recurrent amplifications (for example, DROSHA, YAP1) or homozygous deletions (for example, DDX3X) in OSCC-GB. We find a high proportion of C>G transversions among tobacco users with high numbers of mutations. Many pathways that are enriched for genomic alterations are specific to OSCC-GB. Our work reveals molecular subtypes with distinctive mutational profiles such as patients predominantly harbouring mutations in CASP8 with or without mutations in FAT1. Mean duration of disease-free survival is significantly elevated in some molecular subgroups. These findings open new avenues for biological characterization and exploration of therapies., Gingivo-buccal oral squamous cell carcinoma (OSCC-GB) is the leading cancer among males in India. Here, the authors carry out exome sequencing and recurrence testing in patients with OSCC-GB and highlight genes and biological pathways associated with the disease.
- Published
- 2013