Allelic loss and replication errors at microsatellite loci on chromosome 11p in head and neck squamous carcinoma: association with aggressive biological features.
The frequent loss of heterozygosity (LOH) demonstrated at chromosome 11p regions in several sporadic malignancies has suggested the presence of tumor suppressor genes at these locations. To obtain detailed mapped incidence of the microsatellite alterations at these regions and to investigate the possible correlation between the genotype and the pathobiological characteristics of head and neck squamous carcinoma, we analyzed paired DNA samples from normal mucosa and primary tumor specimens from 56 patients with these tumors. Our results show that 50.9% of the tumors had microsatellite alterations at one or more of these loci. LOH was manifested in 45. 5% and instability in 5.5% of the tumors. 11p15 loci showed more frequent LOH (39.6%) than those of 11p13 (29.3%) and 11p11-12 (18. 8%); the D11S988 (11p15) marker showed the highest single locus incidence of LOH (29.7%). Eight tumors (22.2%) demonstrated simultaneous LOH at both the 11p15 and 11p13 regions. LOH was significantly associated with poor histological differentiation, DNA aneuploidy, and high proliferative activity in these neoplasms. Our study extends the involvement of the 11p13 and 11p15 regions to head and neck squamous tumorigenesis and indicates that the terminal loci of 11p may harbor a tumor suppressor gene(s) associated with the progression of these tumors.
El-Naggar
A K
AK
Departments of Pathology, Experimental Pediatrics, and Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Hurr
K
K
Huff
V
V
Luna
M A
MA
Goepfert
H
H
Batsakis
J G
JG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002880:Chromosomes, Human, Pair 11; D004261:DNA Replication; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged