Data from: Analysis of head and neck carcinoma progression reveals novel and relevant stage-specific changes associated with immortalisation and malignancy

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<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.