Identification of individual genes altered in squamous cell carcinoma of the vulva.
Chromosome rearrangements in squamous cell carcinoma of the vulva (SCV) have indicated common consistent regions of loss and gain. The overall aim of our research was to define and characterize individual genes that underlie the pathogenesis of SCV. Thirteen cell lines from 12 SCV patients were evaluated for loss and gain of 122 genes distributed throughout the genome. Individual genes were analyzed for genetic alterations using a novel genomewide strategy, the multiplex ligation-dependent probe amplification assay. Our candidate gene approach identified several altered loci. Most frequent was the loss of 1 copy of TMSB10, observed in 11 of 12 SCV patients, followed by loss of CTNNB1 and BCL2, which occurred in 7 of 12 patients. Frequent gains/amplifications included CCND1, observed in 8 of 12 patients, and IL12A, in 7 of the 12 patients. Loss and gain of specific genes observed in our study were generally concordant with the results of previous studies of cytogenetics and CGH utilizing the same SCV cell lines. Genetic alterations are hallmarks of tumorigenesis, and there is wide agreement that recurrent altered genomic loci contain genes important for tumor development and progression. Understanding the interplay of cancer genes and the pathways they utilize can lead to the detection of novel molecular targets in the diagnosis, prognosis, and treatment of SCV.
Department of Otolaryngology/Head and Neck Research, Henry Ford Health System, Detroit, Michigan 48202, USA.
Josena P
JP
Kunjoonju
Misa
M
Raitanen
Seija
S
Grénman
Nivedita
N
Tiwari
Maria J
MJ
Worsham
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D005260:Female; D006801:Humans; D014846:Vulvar Neoplasms / Q000235:genetics*