Patterns of chromosomal copy-number alterations in intrahepatic cholangiocarcinoma

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• 作者：Cyril Dalmasso (1)
  Wassila Carpentier (2)
  Catherine Guettier (3) (4)
  Sophie Camilleri-Bro毛t (5)
  Wyllians Vendramini Borelli (4) (6)
  Ced谩lia Rosane Campos dos Santos (4) (6)
  Denis Castaing (3) (4)
  Jean-Charles Duclos-Vall茅e (3) (4)
  Philippe Bro毛t (4) (7) (8)
  
  1. Laboratoire de Math茅matiques et Mod茅lisation d鈥橢vry (LaMME) ; Universit茅 d鈥橢vry Val d鈥橢ssonne ; UMR CNRS 8071 ; USC INRA ; Evry ; France
  2. Plate-forme Post-G茅nomique P3S ; UPMC ; Facult茅 de M茅decine ; Paris ; France
  3. DHU Hepatinov ; Centre H茅pato-Biliaire ; H么pital Paul Brousse ; AP-HP ; Villejuif ; France
  4. Facult茅 de M茅decine ; Univ. Paris-Sud ; Kremlin-Bic锚tre ; France
  5. Department of Pathology ; McGill University ; Montreal ; Canada
  6. Faculdade de Medicina ; Hospital S茫o Lucas da Pontif铆cia Universidade Cat贸lica do Rio Grande do Sul ; Porto Alegre ; Brazil
  7. DHU Hepatinov ; UF Biostatistiques ; H么pital Paul Brousse ; AP-HP ; Villejuif ; France
  8. INSERM UMR-669 ; Villejuif ; France
  
• 关键词：Cholangiocarcinoma ; DNA copy ; number ; Genomic
• 刊名：BMC Cancer
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：15
• 期：1
• 全文大小：1,741 KB
• 参考文献：1. Nakanuma, Y, Curado, M, Franceschi, S, Gores, G, Paradis, V, Sripa, B Intrahepatic cholangiocarcinoma. In: Bosman, FT, HR Carneiro, F, ND, T eds. (2010) WHO Classification of the Tumours of the Digestive System, vol. 2. IARC press, Lyon
  2. Shaib, Y, Davila, J, McGlynn, K, El-Serag, H (2004) Rising incidence of intrahepatic cholangiocarcinoma in the united states: a true increase?. J Hepatol 40: pp. 472-7 CrossRef
  3. Chang, K, Chang, J, Yen, Y (2009) Increasing incidence of intra-hepatic cholangiocarcinoma and its relationship to chronic viral hepatitis. J Natl Compr Canc Netw 7: pp. 423-7
  4. Rizvi, S, Gores, G (2013) Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology 145: pp. 1215-29 CrossRef
  5. Palmer, W, Patel, T (2012) Are common factors involved in the pathogenesis of primary liver cancers? a meta-analysis of risk factors for intrahepatic cholangiocarcinoma. J Hepatol 57: pp. 69-76 CrossRef
  6. Cardinale, V, Semeraro, R, Torrice, A, Gatto, M, Napoli, C, Bragazzi, M (2010) Intra-hepatic and extra-hepatic cholangiocarcinoma: New insight into epidemiology and risk factors. World J Gastrointest Oncol 2: pp. 407-16 CrossRef
  7. Sia, D, Tovar, V, Moeini, A, Llovet, J (2013) Intrahepatic cholangiocarcinoma: pathogenesis and rationale for molecular therapies. Oncogene 32: pp. 4861-70 CrossRef
  8. Andersen, J, Thorgeirsson, S (2012) Genetic profiling of intrahepatic cholangiocarcinoma. Curr Opin Gastroenterol 28: pp. 266-72 CrossRef
  9. Ohashi, K, Tstsumi, M, Nakajima, Y, Nakano, H, Konishi, Y (1996) Ki-ras point mutations and proliferation activity in biliary tract carcinomas. Br J Cancer 74: pp. 930-5 CrossRef
  10. Hahn, S, Bartsch, D, Schroers, A, Galehdari, H, Becker, M, Ramaswamy, A (1998) Mutations of the dpc4/smad4 gene in biliary tract carcinoma. Cancer Res 58: pp. 1124-6
  11. Tannapfel, A, Benicke, M, Katalinic, A, Uhlmann, D, K枚ckerling, F, Hauss, J (2000) Frequency of p16 (ink4a) alterations and k-ras mutations in intrahepatic cholangiocarcinoma of the liver. Gut 47: pp. 721-7 CrossRef
  12. Endo, K, Ashida, K, Miyake, N, Terada, T (2001) E-cadherin gene mutations in human intrahepatic cholangiocarcinoma. J Pathol 193: pp. 310-7 CrossRef
  13. Taniai, M, Higuchi, H, Burgart, L, Gores, G (2002) p16ink4a promoter mutations are frequent in primary sclerosing cholangitis (psc) and psc-associated cholangiocarcinoma. Gastroenterology 123: pp. 1090-8 CrossRef
  14. Terada, T, Nakanuma, Y, Sirica, A (1998) Immunohistochemical demonstration of met overexpression in human intrahepatic cholangiocarcinoma and in hepatolithiasis. Hum Pathol 29: pp. 175-80 CrossRef
  15. Sugimachi, K, Aishima, S, Taguchi, K, Tanaka, S, Shimada, M, Kajiyama, K (2001) The role of overexpression and gene amplification of cyclin d1 in intrahepatic cholangiocarcinoma. J Hepatol 35: pp. 74-9 CrossRef
  16. Ukita, Y, Kato, M, Terada, T (2002) Gene amplification and mrna and protein overexpression of c-erbb-2 (her-2/neu) in human intrahepatic cholangiocarcinoma as detected by fluorescence in situ hybridization, in situ hybridization, and immunohistochemistry. J Hepatol 36: pp. 780-5 CrossRef
  17. AE, S (2008) Role of erbb family receptor tyrosine kinases in intrahepatic cholangiocarcinoma. World J Gastroenterol 14: pp. 7033-58 CrossRef
  18. Andersen, J, Spe, eB, Blechacz, B, Avital, I, Komuta, M, Barbour, A (2012) Genomic and genetic characterization of cholangiocarcinoma identifies therapeutic targets for tyrosine kinase inhibitors. Gastroenterology 142: pp. 1021-31 CrossRef
  19. Sia, D, Hoshida, Y, Villanueva, A, Roayaie, S, Ferrer, J, Tabak, B (2013) Integrative molecular analysis of intrahepatic cholangiocarcinoma reveals 2 classes that have different outcomes. Gastroenterology 144: pp. 829-40 CrossRef
  20. Jiao, Y, Pawlik, T, Anders, R, Selaru, F, Streppel, M, Lucas, D (2013) Exome sequencing identifies frequent inactivating mutations in bap1, arid1a and pbrm1 in intrahepatic cholangiocarcinomas. Nat Genet 45: pp. 1470-3 CrossRef
  21. Borad, M, Champion, M, Egan, J, Liang, W, Fonseca, R, Bryce, A (2014) Integrated genomic characterization reveals novel, therapeutically relevant drug targets in fgfr and egfr pathways in sporadic intrahepatic cholangiocarcinoma. PLoS Genet 10: pp. 1004135 CrossRef
  22. Borger, D, Tanabe, K, Fan, K, Lopez, H, Fantin, V, Straley, K (2012) Frequent mutation of isocitrate dehydrogenase (idh)1 and idh2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist 17: pp. 72-9 CrossRef
  23. Kipp, B, Voss, J, Kerr, S, Barr Fritcher, E, Graham, R, Zhang, L (2012) Isocitrate dehydrogenase 1 and 2 mutations in cholangiocarcinoma. Hum Pathol 43: pp. 1552-8 CrossRef
  24. Zhu, A, Borger, D, Kim, Y, Cosgrove, D, Ejaz, A, Alexandrescu, S (2014) Genomic profiling of intrahepatic cholangiocarcinoma: Refining prognosis and identifying therapeutic targets. Ann Surg Oncol 21: pp. 3827-34 CrossRef
  25. Voss, J, Holtegaard, L, Kerr, S, Fritcher, E, Roberts, L, Gores, G (2013) Molecular profiling of cholangiocarcinoma shows potential for targeted therapy treatment decisions. Hum Pathol 44: pp. 1216-22 CrossRef
  26. Ross, J, Wang, K, Gay, L, Al-Rohil, R, Rand, J, Jones, D (2014) New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next-generation sequencing. Oncologist 19: pp. 235-42 CrossRef
  27. Ong, C, Subimerb, C, Pairojkul, C, Wongkham, S, Cutcutache, I, Yu, W (2012) Exome sequencing of liver fluke-associated cholangiocarcinoma. Nat Genet 44: pp. 690-3 CrossRef
  28. Chan-On, W, Nairism盲gi, M, Ong, C, Lim, W, Dima, S, Pairojkul, C (2013) Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers. Nat Genet 45: pp. 1474-8 CrossRef
  29. Simbolo, M, Fassan, M, Ruzzenente, A, Mafficini, A, LD, W, Corbo, V (2014) Multigene mutational profiling of cholangiocarcinomas identifies actionable molecular subgroups. Oncotarget 5: pp. 2839-52
  30. Arai, Y, Totoki, Y, Hosoda, F, Shirota, T, Hama, N, Nakamura, H (2014) Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma. Hepatology 59: pp. 1427-34 CrossRef
  31. Edge, S, Byrd, D, Compton, C, Fritz, A, Greene, F, Trotti, A (2009) Cancer staging manual. AJCC Cancer Staging Manual. Springer, New York
  32. Illumina. http://www.illumina.com/ .
  33. Peiffer, D, Le, J, Steemers, F, Chang, W, Jenniges, T, Garcia, F (2006) High-resolution genomic profiling of chromosomal aberrations using infinium whole-genome genotyping. Genome Res 16: pp. 1136-48 CrossRef
  34. Pierre-Jean M, Rigaill G, Neuvial P. Performance evaluation of dna copy number segmentation methods. Briefings in Bioinf. 2014. in press.
  35. Gey S, Lebarbier E. Using CART to Detect Multiple Change Points in the Mean for Large Sample. http://hal.archives-ouvertes.fr/hal-00327146/.
  36. Rigaill G. Pruned Dynamic Programming for Optimal Multiple Change-point Detection. http://arxiv.org/abs/1004.0887.
  37. Hartigan, J, Hartigan, P (1985) The dip test of unimodality. Ann Stat 13: pp. 70-84 CrossRef
  38. Broet, P, Tan, P, Alifano, M, Camilleri-Broet, S, Richardson, S (2009) Finding exclusively deleted or amplified genomic areas in lung adenocarcinomas using a novel chromosomal pattern analysis. BMC Med Genomics 2: pp. 43 CrossRef
  39. Toussile, W, Gassiat, E (2009) Model Based Clustering using multilocus data with loci selection. Adv Data Anal Classification 3: pp. 109-34 CrossRef
  R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria
  40. Tyson, G, El-Serag, H (2011) Risk factors for cholangiocarcinoma. Hepatology 54: pp. 173-84 CrossRef
  41. Miller, G, Socci, N, Dhall, D, D鈥橝ngelica, M, DeMatteo, R, Allen, P (2009) Genome wide analysis and clinical correlation of chromosomal and transcriptional mutations in cancers of the biliary tract. J Exp Clin Cancer Res 12: pp. 28-62
  42. Dachrut, S, Banthaisong, S, Sripa, M, Paeyao, A, Ho, C, Lee, S (2009) Dna copy-number loss on 1p36.1 harboring runx3 with promoter hypermethylation and associated loss of runx3 expression in liver fluke-associated intrahepatic cholangiocarcinoma. Asian Pac J Cancer Prev 10: pp. 575-82
  43. Wu, R, Wang, T, Shih, I (2014) The emerging roles of arid1a in tumor suppression. Cancer Biol Ther 15: pp. 655-64 CrossRef
  44. Chou, A, Toon, C, Clarkson, A, Sioson, L, Houang, M, Watson, N (2014) Loss of arid1a expression in colorectal carcinoma is strongly associated with mismatch repair deficiency. Hum Pathol 45: pp. 1697-703 CrossRef
  45. Samartzis, E, Gutsche, K, Dedes, K, Fink, D, Stucki, M, Imesch, P (2014) Loss of arid1a expression sensitizes cancer cells to pi3k- and akt-inhibition. Oncotarget 5: pp. 5295-30
  46. Hollander, M, Maier, C, Hobbs, E, Ashmore, A, Linnoila, R, Dennis, P (2011) Akt1 deletion prevents lung tumorigenesis by mutant k-ras. Oncogene 30: pp. 1812-21 CrossRef
  47. Chen, L, Chan, T, Guan, X (2010) Chromosome 1q21 amplification and oncogenes in hepatocellular carcinoma. Acta Pharmacol Sin 31: pp. 1165-71 CrossRef
  48. Leone, F, Cavalloni, G, Pignochino, Y, Sarotto, I, Ferraris, R, Piacibello, W (2006) Somatic mutations of epidermal growth factor receptor in bile duct and gallbladder carcinoma. Clin Cancer Res 12: pp. 1680-5 CrossRef
  49. Miyamoto, M, Ojima, H, Iwasaki, M, Shimizu, H, Kokubu, A, Hiraoka, N (2011) Prognostic significance of overexpression of c-met oncoprotein in cholangiocarcinoma. Br J Cancer 105: pp. 131-8 CrossRef
  
• 刊物主题：Cancer Research; Oncology; Stem Cells; Animal Models; Internal Medicine;
• 出版者：BioMed Central
• ISSN：1471-2407

文摘

Background Intrahepatic cholangiocarcinomas (ICC) are relatively rare malignant tumors associated with a poor prognosis. Recent studies using genome-wide sequencing technologies have mainly focused on identifying new driver mutations. There is nevertheless a need to investigate the spectrum of copy number aberrations in order to identify potential target genes in the altered chromosomal regions. The aim of this study was to characterize the patterns of chromosomal copy-number alterations (CNAs) in ICC. Methods 53 patients having ICC with frozen material were selected. In 47 cases, DNA hybridization has been performed on a genomewide SNP array. A procedure with a segmentation step and a calling step classified genomic regions into copy-number aberration states. We identified the exclusively amplified and deleted recurrent genomic areas. These areas are those showing the highest estimated propensity level for copy loss (resp. copy gain) together with the lowest level for copy gain (resp. copy loss). We investigated ICC clustering. We analyzed the relationships between CNAs and clinico-pathological characteristics. Results The overall genomic profile of ICC showed many alterations with higher rates for the deletions. Exclusively deleted genomic areas were 1p, 3p and 14q. The main exclusively amplified genomic areas were 1q, 7p, 7q and 8q. Based on the exclusively deleted/amplified genomic areas, a clustering analysis identified three tumors groups: the first group characterized by copy loss of 1p and copy gain of 7p, the second group characterized by 1p and 3p copy losses without 7p copy gain, the last group characterized mainly by very few CNAs. From univariate analyses, the number of tumors, the size of the largest tumor and the stage were significantly associated with shorter time recurrence. We found no relationship between the number of altered cytobands or tumor groups and time to recurrence. Conclusion This study describes the spectrum of chromosomal aberrations across the whole genome. Some of the recurrent exclusive CNAs harbor candidate target genes. Despite the absence of correlation between CNAs and clinico-pathological characteristics, the co-occurence of 7p gain and 1p loss in a subgroup of patients may suggest a differential activation of EGFR and its downstream pathways, which may have a potential effect on targeted therapies.