Prognostic significance of microsatellite alterations at 1p36 in cholangiocarcinoma.
OBJECTIVE
To investigate loss of heterozygosity (LOH) and microsatellite instability (MSI) on the chromosomal region 1p36-pter in cholangiocarcinoma (CCA) patients and determine the association between microsatellite alterations and clinicopathological parameters.


METHODS
Ten polymorphic microsatellite markers were determined for LOH and MSI using GS-3000 gel scan fragment autoanalyzer.


RESULTS
Sixty-eight out of 90 cases (75.6%) showed LOH in one or more loci. LOH was found most frequently at D1S199 (40.0%), D1S507 (34.6%), D1S2845 (30.5%), and D1S2734 (30.1%). MSI was found in 34 of 90 cases (37.8%) at one or more loci. Fine mapping at 1p36 showed two distinctive regions of common loss, which were D1S2845 and the 25.5-cM region between D1S507 and D1S2734, indicating the existence of putative tumor suppressor genes that is likely to play important roles in the development of CCA. Patients with LOH at D1S234 showed less lymphatic invasion (P = 0.017), whereas patients with LOH at D1S2676 exhibited more lymphatic invasion than those without (P = 0.031). LOH at D1S2845 showed a significant correlation with nerve invasion (P = 0.029). Moreover, patients who demonstrated MSI at D1S228 showed a poor prognosis (P = 0.0026).


CONCLUSIONS
Allelic loss plays a major role in microsatellite alterations at chromosome 1p36, which may contribute to carcinogenesis and pathogenesis of liver fluke related CCA and these alterations can be used as molecular prognostic indicators for CCA patients.
Limpaiboon
Temduang
T
Department of Clinical Chemistry, Center for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand. temduang@kku.ac.th
Tapdara
Sumonta
S
Jearanaikoon
Patcharee
P
Sripa
Banchob
B
Bhudhisawasdi
Vajarabhongsa
V
D000483:Alleles; D000818:Animals; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000469:parasitology / Q000473:pathology*; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D043171:Chromosomal Instability / Q000235:genetics; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D003851:Deoxyribonucleases / Q000235:genetics / Q000502:physiology; D018450:Disease Progression; D005210:Fasciola hepatica / Q000472:pathogenicity; D005213:Fascioloidiasis / Q000150:complications / Q000175:diagnosis / Q000473:pathology; D016147:Genes, Tumor Suppressor / Q000502:physiology; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000502:physiology
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D014157:Transcription Factors; D011495:Histone-Lysine N-Methyltransferase; C093563:PRDM2 protein, human; C113696:DFFB protein, human; D003851:Deoxyribonucleases; D020764:cdc42 GTP-Binding Protein