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High resolution chromosome 3p, 8p, 9q and 22q allelotyping analysis in the pathogenesis of gallbladder carcinoma.

Wistuba II, Maitra A, Carrasco R, Tang M, Troncoso P, Minna JD, Gazdar AF - Br. J. Cancer (2002)

Bottom Line: Allele losses were frequently detected in normal and dysplastic gallbladder epithelia.There was a progressive increase of the overall loss of heterozygosity frequency with increasing severity of histopathological changes.Allele losses were not random and followed a sequence.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomic Pathology, Pontificia Universidad Catolica de Chile, Marcoleta 367, P.O. Box 114-D, Santiago, Chile. iwistuba@med.puc.cl

ABSTRACT
Our recent genome-wide allelotyping analysis of gallbladder carcinoma identified 3p, 8p, 9q and 22q as chromosomal regions with frequent loss of heterozygosity. The present study was undertaken to more precisely identify the presence and location of regions of frequent allele loss involving those chromosomes in gallbladder carcinoma. Microdissected tissue from 24 gallbladder carcinoma were analysed for PCR-based loss of heterozygosity using 81 microsatellite markers spanning chromosome 3p (n=26), 8p (n=14), 9q (n=29) and 22q (n=12) regions. We also studied the role of those allele losses in gallbladder carcinoma pathogenesis by examining 45 microdissected normal and dysplastic gallbladder epithelia accompanying gallbladder carcinoma, using 17 microsatellite markers. Overall frequencies of loss of heterozygosity at 3p (100%), 8p (100%), 9q (88%), and 22q (92%) sites were very high in gallbladder carcinoma, and we identified 13 distinct regions undergoing frequent loss of heterozygosity in tumours. Allele losses were frequently detected in normal and dysplastic gallbladder epithelia. There was a progressive increase of the overall loss of heterozygosity frequency with increasing severity of histopathological changes. Allele losses were not random and followed a sequence. This study refines several distinct chromosome 3p, 8p, 9q and 22q regions undergoing frequent allele loss in gallbladder carcinoma that will aid in the positional identification of tumour suppressor genes involved in gallbladder carcinoma pathogenesis.

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Patterns of chromosome 3p allele losses in gallbladder carcinoma. The cases have been arranged from left to right in decreasing order of chromosome 3p allele losses. Markers are placed in the predicted order from 3pter-cen. Four regions (R1–R4) having frequent allelic losses are shown. Lower panel: seven autoradiographs showing discrete allele loss at chromosome 3p in a microdissected GBC case (case 8) demonstrating loss and retention of neighbouring alleles. L, lymphocytes or normal stromal cells; T, microdissected invasive GBC. Horizontal bars on the left of the autoradiographs indicate the main allelic bands.
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fig2: Patterns of chromosome 3p allele losses in gallbladder carcinoma. The cases have been arranged from left to right in decreasing order of chromosome 3p allele losses. Markers are placed in the predicted order from 3pter-cen. Four regions (R1–R4) having frequent allelic losses are shown. Lower panel: seven autoradiographs showing discrete allele loss at chromosome 3p in a microdissected GBC case (case 8) demonstrating loss and retention of neighbouring alleles. L, lymphocytes or normal stromal cells; T, microdissected invasive GBC. Horizontal bars on the left of the autoradiographs indicate the main allelic bands.

Mentions: To evaluate LOH on GBC, we used primers flanking 81 microsatellite repeat polymorphisms spanning several 3p (n=26), 8p (n=14), 9q (n=29) and 22q (n=12) regions showing high frequencies of LOH in the genome-wide allelotyping analysis on GBC (Wistuba et al, 2001). The microsatellite markers tested are shown in Figures 2Figure 2


High resolution chromosome 3p, 8p, 9q and 22q allelotyping analysis in the pathogenesis of gallbladder carcinoma.

Wistuba II, Maitra A, Carrasco R, Tang M, Troncoso P, Minna JD, Gazdar AF - Br. J. Cancer (2002)

Patterns of chromosome 3p allele losses in gallbladder carcinoma. The cases have been arranged from left to right in decreasing order of chromosome 3p allele losses. Markers are placed in the predicted order from 3pter-cen. Four regions (R1–R4) having frequent allelic losses are shown. Lower panel: seven autoradiographs showing discrete allele loss at chromosome 3p in a microdissected GBC case (case 8) demonstrating loss and retention of neighbouring alleles. L, lymphocytes or normal stromal cells; T, microdissected invasive GBC. Horizontal bars on the left of the autoradiographs indicate the main allelic bands.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376134&req=5

fig2: Patterns of chromosome 3p allele losses in gallbladder carcinoma. The cases have been arranged from left to right in decreasing order of chromosome 3p allele losses. Markers are placed in the predicted order from 3pter-cen. Four regions (R1–R4) having frequent allelic losses are shown. Lower panel: seven autoradiographs showing discrete allele loss at chromosome 3p in a microdissected GBC case (case 8) demonstrating loss and retention of neighbouring alleles. L, lymphocytes or normal stromal cells; T, microdissected invasive GBC. Horizontal bars on the left of the autoradiographs indicate the main allelic bands.
Mentions: To evaluate LOH on GBC, we used primers flanking 81 microsatellite repeat polymorphisms spanning several 3p (n=26), 8p (n=14), 9q (n=29) and 22q (n=12) regions showing high frequencies of LOH in the genome-wide allelotyping analysis on GBC (Wistuba et al, 2001). The microsatellite markers tested are shown in Figures 2Figure 2

Bottom Line: Allele losses were frequently detected in normal and dysplastic gallbladder epithelia.There was a progressive increase of the overall loss of heterozygosity frequency with increasing severity of histopathological changes.Allele losses were not random and followed a sequence.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomic Pathology, Pontificia Universidad Catolica de Chile, Marcoleta 367, P.O. Box 114-D, Santiago, Chile. iwistuba@med.puc.cl

ABSTRACT
Our recent genome-wide allelotyping analysis of gallbladder carcinoma identified 3p, 8p, 9q and 22q as chromosomal regions with frequent loss of heterozygosity. The present study was undertaken to more precisely identify the presence and location of regions of frequent allele loss involving those chromosomes in gallbladder carcinoma. Microdissected tissue from 24 gallbladder carcinoma were analysed for PCR-based loss of heterozygosity using 81 microsatellite markers spanning chromosome 3p (n=26), 8p (n=14), 9q (n=29) and 22q (n=12) regions. We also studied the role of those allele losses in gallbladder carcinoma pathogenesis by examining 45 microdissected normal and dysplastic gallbladder epithelia accompanying gallbladder carcinoma, using 17 microsatellite markers. Overall frequencies of loss of heterozygosity at 3p (100%), 8p (100%), 9q (88%), and 22q (92%) sites were very high in gallbladder carcinoma, and we identified 13 distinct regions undergoing frequent loss of heterozygosity in tumours. Allele losses were frequently detected in normal and dysplastic gallbladder epithelia. There was a progressive increase of the overall loss of heterozygosity frequency with increasing severity of histopathological changes. Allele losses were not random and followed a sequence. This study refines several distinct chromosome 3p, 8p, 9q and 22q regions undergoing frequent allele loss in gallbladder carcinoma that will aid in the positional identification of tumour suppressor genes involved in gallbladder carcinoma pathogenesis.

Show MeSH
Related in: MedlinePlus