Losses of heterozygosity on chromosomes 17p and 9p/18q may play important roles in early and advanced phases of gallbladder carcinogenesis.
OBJECTIVE
This present study aimed to investigate the genetic changes in gallbladder carcinogenesis.


METHODS
Eleven intramucosal gallbladder carcinomas were compared with 31 invasive lesions for loss of heterozygosity (LOH) on chromosomes 5q, 9p, 17p and 18q, frame-shift mutations in a ten-adenine repeat site within the gene encoding the transforming growth factor beta type II receptor (TGFbetaRII) and an eight-guanine repeat site within BAX, and point mutations in codon 12 of Ki-ras.


RESULTS
The incidences of LOH in intramucosal and invasive carcinomas were 14% and 17% on 5q, 9% and 52% on 9p, 64% and 65% on 17p, and 13% and 32% on 18q. No frame-shift mutations were found at TGFbetaRII or BAX, and point mutations in codon 12 of Ki-ras were present in only 8% of the samples. Thus, LOH on 17p was by far the most frequent lesion with similar results in both intramucosal and invasive carcinomas. In contrast, the frequency of LOH on 9p and 18q was distinctly higher in invasive lesions.


CONCLUSIONS
The present data suggest that LOH on 17p may play an important role in the evolution of gallbladder carcinoma from a relatively early phase, while LOH on 9p and 18q may play roles in progression.
Hidaka
E
E
Department of Pathology, Cancer Institute, Tokyo, Japan.
Yanagisawa
A
A
Sakai
Y
Y
Seki
M
M
Kitagawa
T
T
Setoguchi
T
T
Kato
Y
Y
D000225:Adenine / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000473:pathology; D011905:Genes, ras / Q000235:genetics*; D006147:Guanine / Q000378:metabolism; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction / Q000379:methods; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D051028:bcl-2-Associated X Protein; D018631:ras Proteins / Q000235:genetics*
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018125:Receptors, Transforming Growth Factor beta; D051028:bcl-2-Associated X Protein; D006147:Guanine; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018631:ras Proteins; D000225:Adenine