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. 2006 Jul 21;12(27):4377-82.
doi: 10.3748/wjg.v12.i27.4377.

Prognostic significance of microsatellite alterations at 1p36 in cholangiocarcinoma

Temduang Limpaiboon  1 , Sumonta Tapdara, Patcharee Jearanaikoon, Banchob Sripa, Vajarabhongsa Bhudhisawasdi
Affiliations

Prognostic significance of microsatellite alterations at 1p36 in cholangiocarcinoma

Temduang Limpaiboon et al. World J Gastroenterol. .

Abstract

Aim: 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).

Conclusion: 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.

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Figures

Figure 1
Figure 1
Representative examples of LOH and MSI at various loci of chromosome 1p36 (L, leucocyte DNA; T, tumor DNA). Arrows indicate the abnormalities
Figure 2
Figure 2
LOH and MSI frequencies at each locus of chromosome 1p36-pter.
Figure 3
Figure 3
Fine mapping of the chromosome 1p36-pter in 90 CCA. The common loss regions were located at D1S2845 and the 25.5-cM region between D1S507 and D1S2734.
Figure 4
Figure 4
The Kaplan-Meier survival curves showed a poor prognosis in patients who demonstrated MSI at D1S228. Non informative cases were excluded.
See this image and copyright information in PMC

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