Fractional allele loss indicates distinct genetic populations in the development of squamous cell carcinoma of the head and neck (SCCHN)

Abstract

Loss of heterozygosity (LOH) had been widely used to assess genetic instability in tumours and a high LOH on chromosome arms 3p, 9p and 17p has been considered to be a common event in squamous cell carcinoma of the head and neck (SCCHN). We have investigated LOH in 52 SCCHN using a range of microsatellite markers. LOH was observed in 69% of individuals on 17p using seven markers, in 64% of individuals on 3p using 17 markers and in 61% of individuals on 9p using 11 markers. Fractional allele loss (FAL) has been calculated for each tumour (FAL is the number of chromosomal arms showing LOH divided by the number of informative chromosomal arms) and a median FAL value of 0.25 was obtained in the 52 SCCHN studied. The LOH data were examined on the basis of FAL scores: low FAL (LFAL), 0.00-0.19; medium FAL (MFAL), 0.20-0.32; high FAL (HFAL), 0.33-0.88. HFAL tumours demonstrated a significantly higher LOH on chromosome arms 3p, 9p and 17p, with 94% LOH on 3p, 94% on 9p and 100% on 17p compared with LFAL tumours. Six of the 16 patients in the LFAL group were found to have no LOH on 3p, 9p or 17p and of these four had LOH at other sites, on chromosomes 2p25-p24, 5q21-22, 7pter-p22, 8q13-q22.1, 11q23.3, 13q32, 17q, 18p11.21, 18q21.31 and 19q12-q13.1. These results indicate that LFAL patients form a subset of SCCHN tumours with distinct molecular initiating events which may represent a discrete genetic population.

Molecular Cloning and Characterization of RNF26 on Human Chromosome 11q23 Region, Encoding a Novel RING Finger Protein with Leucine Zipper

“…As the 11q23 region is frequently deleted in squamous cell carcinoma of head and neck (14), expression and copy number of the RNF26 gene in 12 esophageal cancer cell lines were investigated. The 3.2-kb RNF26 mRNA was detected in all esophageal cancer cell lines examined in this study (Fig.…”

“…Multiple regions within human chromosome 11q23 are frequently deleted or translocated in several types of human cancer, including leukemia (10), breast cancer (11), lung cancer (12), cervical uterus cancer (13), squamous cell carcinoma of head and neck (14), melanoma (15), and colorectal cancer (16). Recently, I have cloned and characterized the MFRP gene on 11q23 region, encoding a membrane-type Frizzled-related protein (17).…”

Altered plakoglobin expression at mRNA and protein levels correlates with clinical outcome in patients with oropharynx squamous carcinomas

“…A new tumor-suppressor gene has been identified by allelic loss on chromosome 17. 31 Abnormalities in chromosome 17 are frequently associated with head and neck SCC. 31 Because plakoglobin is located on chromosome 17, band q12-q21, 17,32 it is a good candidate for this tumor-suppressor gene.…”

“…31 Abnormalities in chromosome 17 are frequently associated with head and neck SCC. 31 Because plakoglobin is located on chromosome 17, band q12-q21, 17,32 it is a good candidate for this tumor-suppressor gene. Moreover, loss of heterozygosity on chromosome 17 is observed in breast and ovarian cancers, 17 suggesting that plakoglobin may function as a generalized tumor-suppressor gene in man.…”

Allelic loss at 19q12 and Xq11–12 predict an adverse clinical outcome in patients with mucinous ovarian tumours of low malignant potential

“…Although deletions of chromosome 19q12 have been reported in head and neck carcinoma, gliolbastoma, and astrocytoma, the association of LOH at that region with poor survival has not been reported previously (Nunn et al, 1999;Hu et al, 2002;Beder et al, 2003). We speculate that a candidate tumour suppressor gene in the 19q12 region is associated not only with tumour progression but also with an aggressive clinical phenotype.…”