Prognostic value of DNA alterations on chromosome 17p13.2 for intrahepatic cholangiocarcinoma.
OBJECTIVE
To characterize and evaluate DNA alterations among intrahepatic cholangiocarcinoma (ICC) patients.


METHODS
DNA from tumor and corresponding normal tissues of 52 patients was amplified with 33 arbitrary primers. The DNA fragment that alters most frequently in ICC was cloned, sequenced, and identified by comparison with known nucleotide sequences in the genome database (www.ncbi.nlm.nih.gov). The DNA copy numbers of the allelic alterations in cholangiocarcinoma were determined by quantitative real-time PCR and interpreted as allelic loss or DNA amplification by comparison with the reference gene. Associations between allelic imbalance and clinicopathological parameters of ICC patients were evaluated by chi2-test. The Kaplan-Meier method was used to analyze survival rates.


RESULTS
From 33 primers, an altered DNA fragment (518 bp) amplified from BC17 random primer was found frequently in the tumors analyzed and mapped to chromosome 17p13.2. Sixteen of 52 (31%) cases showed DNA amplification, while 7 (13%) showed allelic loss. Interestingly, DNA amplification on chromosome 17p13.2 was associated with a good prognosis, median survival time (wk) of amp vs no amp was 44.14 vs 24.14, P = 0.002; whereas allelic loss of this DNA sequence corresponded with a poor prognosis, median survival time (wk) of loss vs no loss was 18.00 vs 28.71, P = 0.019). Moreover, Kaplan-Meier curves comparing the DNA alterations with survival depicted highly significant separation that the median survival time equal to DNA amplification, allelic loss, and normal was 44.14 wk, 18.00 wk, and 24.29 wk, respectively (P = 0.005).


CONCLUSIONS
Alterations in the DNA sequence on chromosome 17p13.2 may be involved in cholangio-carcinogenesis, and could be used as a prognostic marker in the treatment of ICC patients.
Chuensumran
Ubol
U
Department of Tropical Nutrition and Food Science, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
Wongkham
Sopit
S
Pairojkul
Chawalit
C
Chauin
Siri
S
Petmitr
Songsak
S
D000328:Adult; D000368:Aged; D022981:Allelic Imbalance / Q000235:genetics; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000235:genetics*; D001653:Bile Ducts, Intrahepatic; D016022:Case-Control Studies; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques; D011379:Prognosis
D004273:DNA, Neoplasm