Recurrent cytogenetic abnormalities in squamous cell carcinomas of the head and neck region

Abstract

We characterized the breakpoints, gains, and losses of chromosome material in squamous cell carcinomas of the head and neck region from 29 patients. Cell lines were karyotyped in 1/3 of cases, direct preparations or early in vitro harvests in 1/3, and both in 1/3 of cases. GTG-banding was employed in all cases, as were C-banding and RBG- and AgNOR-staining in most. Some tumors were near-diploid and others near-tetraploid, but many had mixed populations, with diploid, tetraploid, and octoploid subclones representing essentially the same karyotypic pattern. The most frequent changes were deletions. Losses affecting 3p13-p24, 5q12-q23, 8p22-p23, 9p21-p24, and 18q22-q23 ranged in frequency from 40% to 60% of tumors. Loss of the short arm of the inactive X occurred in 70% of tumors from female patients, and loss or rearrangement of the Y occurred in 74% of tumors from male patients. Loss of 18q appeared to be associated with short survival, as did the presence of multiple deletions. There was gain (2-5 extra copies) of 3q21-qter, 5p, 7p, 8q, and 11q13-q23 in 28-38% of tumors. Three tumors had an hsr involving 11q13-q21. Gain of material at 11q13 is postulated to be associated with amplification of the PRADI/CCND gene at that locus. A translocation between proximal 1p and either an acrocentric short arm or proximal 8p or 9p was observed in squamous cell carcinomas of the head and neck region but not in female genital tract tumors. No other abnormalities appeared to be site specific, suggesting a pattern of genetic evolution in squamous cell carcinoma that is independent of anatomic site.

Amplification, increased dosage and in situ expression of the telomerase RNA gene in human cancer

“…These data are consistent with the chromosome 3 data from karyotypic and CGH analysis of SCC-HN and cervical cancer Hermsen et al, 1996;Heselmeyer et al, 1996;Speicher et al, 1995;Sreekantaiah et al, 1994;Van Dyke et al, 1994) and suggest dysregulation of hTR expression may occur by a number of genetic routes including ampli®cation, polysomy and isochromosome 3q formation. Thus, possible mechanisms of telomerase activation and escape from senescence, include imbalance between gain of hTR copies and the loss or titration out of telomerase repressors, for example isochromosome 3q would result in loss of the chromosome 3p repressor, (Ohmura et al, 1995) with a gain of one copy of hTR.…”

p16MTS1/CDK4I mutations and concomitant loss of heterozygosity at 9p21-23 are frequent events in squamous cell carcinoma of the larynx

“…Case 421 showed a 4.3 kb fragment indicating that the SacII sites at exon 1 were methylated. Lane labeled EcoRI corresponds to genomic DNA restricted only with EcoRI showing the expected 4.3 kb fragment p16 MTS1/CDK4I in laryngeal carcinomas P Jares et al cytogenetic and microsatellite studies had detected 9p allelic losses in 40 ± 72% of head and neck tumors with a minimal common region around 9p21 Van Dyke et al, 1994). More recently, LOH at 9p21 has also been detected in preinvasive lesions of head and neck tumors and premalignant lesions of oral mucosa suggesting that this genetic alteration is an early event in the progression of SCC of this region (Mao et al, 1996;.…”

Impairment of MLH1 and CDKN2A in oncogenesis of laryngeal cancer

“…The karyotypes in HNSCC were shown to be complex with breakpoints underlying chromosomal alterations located mainly at 1p, 1q, 3p, 3q, 4q, 8p, 8q, 9p, 10p, 10q, 11q, 13p, 14p, 15p and 15q. Nonrandom patterns of chromosomal aberrations in the progression of HNSCC have been suggested (Jin et al, 1990;Van Dyke et al, 1994;Soder et al, 1995). Isochromosomes 8q, deletion 3p and homogenously staining regions at 11q13 were most often observed among the recurrent structural chromosomal aberrations (Van Dyke et al, 1994;Soder et al, 1995;Bergamo et al, 2000).…”

“…Nonrandom patterns of chromosomal aberrations in the progression of HNSCC have been suggested (Jin et al, 1990;Van Dyke et al, 1994;Soder et al, 1995). Isochromosomes 8q, deletion 3p and homogenously staining regions at 11q13 were most often observed among the recurrent structural chromosomal aberrations (Van Dyke et al, 1994;Soder et al, 1995;Bergamo et al, 2000). The application of comparative genomic hybridisation (CGH) permitted the identification of chromosomal imbalances (Kujawski et al, 1999;Bergamo et al, 2000).…”