DOI: 10.5061/dryad.314k5k5
title: Data from: Analysis of head and neck carcinoma progression reveals novel and relevant stage-specific changes associated with immortalisation and malignancy

description: Head and neck squamous cell carcinoma (HNSCC) is a widely prevalent cancer
 globally with high mortality and morbidity. We report here changes in the
 genomic landscape in the development of these tumours from potentially
 premalignant lesions (PPOLS) to malignancy and lymph node metastases.
 Frequent likely pathological mutations are restricted to a relatively
 small set of genes including TP53, CDKN2A, FBXW7, FAT1, NOTCH1 and KMT2D;
 these arise early in tumour progression and are present in PPOLs with
 NOTCH1 mutations restricted to cell lines from lesions that subsequently
 progressed to HNSCC. The most frequent genetic changes are of consistent
 somatic copy number alterations (SCNA). The earliest SCNAs involved
 deletions of CSMD1 (8p23.2), FHIT (3p14.2) and CDKN2A (9p21.3) together
 with gains of chromosome 20. CSMD1 deletions or promoter hypermethylation
 were present in all of the immortal PPOLs and occurred at high frequency
 in the immortal HNSCC cell lines (promoter hypermethylation ~63%,
 hemizygous deletions ~75%, homozygous deletions ~18%). Forced expression
 of CSMD1 in the HNSCC cell line H103 showed significant suppression of
 proliferation (p=0.0053) and invasion in vitro (p=5.98X10-5) supporting a
 role for CSMD1 inactivation in early head and neck carcinogenesis. In
 addition, knockdown of CSMD1 in the CSMD1-expressing BICR16 cell line
 showed significant stimulation of invasion in vitro (p=1.82 x 10-5) but
 not cell proliferation (p=0.239). HNSCC with and without nodal metastases
 showed some clear differences including high copy number gains of CCND1,
 hsa-miR-548k and TP63 in the metastases group. GISTIC peak SCNA regions
 showed significant enrichment (adj P&lt;0.01) of genes in multiple
 KEGG cancer pathways at all stages with disruption of an increasing number
 of these involved in the progression to lymph node metastases. Sixty-seven
 genes from regions with statistically significant differences in SCNA/LOH
 frequency between immortal PPOL and HNSCC cell lines showed correlation
 with expression including 5 known cancer drivers.
description: SNP ARRAY NEXUS
 BIODISCOVERY DATAData output from SNP
 Array analyses in Nexus Copy Number v7.5 (BioDiscovery, Inc.). Data per
 sample includes: Calls.txt; call thresholds.txt; descriptor set;
 probes.ivg; raw_snps.text; raw.txt; segments.ivg; setting.xmle; snps.ivg;
 snpsegments.ivg; zygoisty.txt; zygositythreshold.txt;PROBE DATA - ALL
 SAMPLESData output from SNP
 Array analyses in Nexus Copy Number v7.5 (BioDiscovery, Inc.). Probe data
 per chromosome for all samplesCOPY NUMBER ANALYSES -
 SAMPLE SUMMARY AND TYPESample details for copy
 number analysesSAMPLE SUMMARY AND
 TYPE.txtIllumina HumanHap550
 genotyping dataSNP genotyping data in
 binary file formatHaloplex fastq
 filesFastq files containing
 the Haloplex reads.haloplex_fastq.tar.gzWS51615_12007521_Agi_Ex_2.sorted.nodup.bamWS51615_12007523_Agi_Ex_3.sorted.nodup.bamWS51615_12007524_Agi_Ex_4.sorted.nodup.bamWS51615_12007525_Agi_Ex_5.sorted.nodup.bamWS51615_12007526_Agi_Ex_6.sorted.nodup.bamWS51615_12007527_Agi_Ex_7.sorted.nodup.bamWS51615_12007528_Agi_Ex_8.sorted.nodup.bamWS51615_12007529_Agi_Ex_9.sorted.nodup.bamWS51615_12007530_Agi_Ex_10.sorted.nodup.bamSEQUENCING VARIANTSSEQUENCING VARIANTS IDENTIFIED FROM EXOME AND TARGETED HALOPLEX CAPTURES. RAW DATA AND SAMPLES FILTERED TO REMOVE VARIANTS WITH ExAC POPULATION ALTERNATE ALLELE FREQUENCY OF &lt;0.5.