title: Integrated genomics approach to identify biologically relevant alterations in fewer samples.
abstract: BACKGROUND
  Several statistical tools have been developed to identify genes mutated at rates significantly higher than background, indicative of positive selection, involving large sample cohort studies. However, studies involving smaller sample sizes are inherently restrictive due to their limited statistical power to identify low frequency genetic variations.
  
  
  RESULTS
  We performed an integrated characterization of copy number, mutation and expression analyses of four head and neck cancer cell lines - NT8e, OT9, AW13516 and AW8507 - by applying a filtering strategy to prioritize for genes affected by two or more alterations within or across the cell lines. Besides identifying TP53, PTEN, HRAS and MET as major altered HNSCC hallmark genes, this analysis uncovered 34 novel candidate genes altered. Of these, we find a heterozygous truncating mutation in Nuclear receptor binding protein, NRBP1 pseudokinase gene, identical to as reported in other cancers, is oncogenic when ectopically expressed in NIH-3 T3 cells. Knockdown of NRBP1 in an oral carcinoma cell line bearing NRBP1 mutation inhibit transformation and survival of the cells.
  
  
  CONCLUSIONS
  In overall, we present the first comprehensive genomic characterization of four head and neck cancer cell lines established from Indian patients. We also demonstrate the ability of integrated analysis to uncover biologically important genetic variation in studies involving fewer or rare clinical specimens.
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Center, Navi Mumbai, Maharashtra, 410210, India. pratikchandrani@gmail.com.
authors.forename: Pratik
authors.initials: P
authors.lastname: Chandrani
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Center, Navi Mumbai, Maharashtra, 410210, India. pawanupadhyay70@gmail.com.
authors.forename: Pawan
authors.initials: P
authors.lastname: Upadhyay
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Center, Navi Mumbai, Maharashtra, 410210, India. prajish89@gmail.com.
authors.forename: Prajish
authors.initials: P
authors.lastname: Iyer
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Center, Navi Mumbai, Maharashtra, 410210, India. tannamayur90@gmail.com.
authors.forename: Mayur
authors.initials: M
authors.lastname: Tanna
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Center, Navi Mumbai, Maharashtra, 410210, India. madhurshetty1986@gmail.com.
authors.forename: Madhur
authors.initials: M
authors.lastname: Shetty
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Center, Navi Mumbai, Maharashtra, 410210, India. raghuram.venkata@gmail.com.
authors.forename: Gorantala Venkata
authors.initials: GV
authors.lastname: Raghuram
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Center, Navi Mumbai, Maharashtra, 410210, India. ninadoak@gmail.com.
authors.forename: Ninad
authors.initials: N
authors.lastname: Oak
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Center, Navi Mumbai, Maharashtra, 410210, India. ankita0007@gmail.com.
authors.forename: Ankita
authors.initials: A
authors.lastname: Singh
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Center, Navi Mumbai, Maharashtra, 410210, India. rohanchaubal@gmail.com.
authors.forename: Rohan
authors.initials: R
authors.lastname: Chaubal
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Center, Navi Mumbai, Maharashtra, 410210, India. mnj.rmtk@gmail.com.
authors.forename: Manoj
authors.initials: M
authors.lastname: Ramteke
authors.affiliation: Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Center, Mumbai, Maharashtra, India. sudeepgupta04@yahoo.com.
authors.forename: Sudeep
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Center, Navi Mumbai, Maharashtra, 410210, India. adutt@actrec.gov.in.
authors.forename: Amit
authors.initials: A
authors.lastname: Dutt
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004273:DNA, Neoplasm; D018628:Gene Dosage; D023281:Genomics / Q000379:methods*; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D059785:Karyotype; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D017422:Sequence Analysis, DNA; D000077195:Squamous Cell Carcinoma of Head and Neck; D059467:Transcriptome; D033921:Vesicular Transport Proteins / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; C410809:NRBP1 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D033921:Vesicular Transport Proteins