Frequent loss of heterozygosity for Rb, TP53, and chromosome arm 3p, but not NME1 in squamous cell carcinomas of the supraglottic larynx.
BACKGROUND
The inactivation of some tumor suppressor genes classically manifests itself through the loss of heterozygosity at nearby genetic mapping markers. Inactivation of these genes appears to have diagnostic/prognostic significance in some types of tumors. Molecular genetic tools based on suppressor inactivation might, therefore, have great utility in treatment planning.


METHODS
The polymerase chain reaction and highly informative microsatellite markers were used to compare DNA derived from matched sets of tumor and normal tissue samples from 37 supraglottic laryngeal squamous cell carcinomas. Tumor samples were microdissected free of contaminating normal tissue to maximize the detection of allelic loss. Polymerase chain reaction products were fractionated by denaturing gel electrophoresis and were visualized by autoradiography.


RESULTS
Allelic losses were frequent at TP53 (56% of the tumors), the retinoblastoma gene (Rb, 59%), and the p13-14 region of chromosome 3 (64%). In contrast, the putative metastasis suppressor, NME1 (also known as NM23), was lost infrequently (7%). NME1 allelic loss did not correlate with the presence of lymph node metastases in these patients.


CONCLUSIONS
The high frequencies of allelic loss at TP53, Rb, and 3p13-14 suggest that these suppressors play a major role in laryngeal carcinogenesis. In sharp contrast, the low frequency of loss at NME1 and its equal distribution in nodal metastasis-positive and -negative patients suggests that inactivation of this gene by allelic loss probably does not play a role in the development of regional metastases from these tumors. Allelic loss in 3p13-14 was found in tumors of all histopathologic grades.
Scholnick
S B
SB
Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri 63110.
Sun
P C
PC
Shaw
M E
ME
Haughey
B H
BH
el-Mofty
S K
SK
D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D004273:DNA, Neoplasm / Q000032:analysis; D016161:Genes, Retinoblastoma; D016158:Genes, p53; D006579:Heterozygote; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000032:analysis*
D004273:DNA, Neoplasm; D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins