Molecular cytogenetic characterization of pancreas cancer cell lines reveals high complexity chromosomal alterationsGriffin C.A.a, b · Morsberger L.a · Hawkins A.L.a · Haddadin M.a · Patel A.a · Ried T.c · Schrock E.c · Perlman E.J.a · Jaffee E.b
Departments of aPathology and bOncology, Johns Hopkins University, Baltimore; cNHGRI, Bethesda, MD (USA)
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Karyotype analysis can provide clues to significant genes involved in the genesis and growth of pancreas cancer. The genome of pancreas cancer is complex, and G-band analysis cannot resolve many of the karyotypic abnormalities seen. We studied the karyotypes of 15 recently established cell lines using molecular cytogenetic tools. Comparative genomic hybridization (CGH) analysis of all 15 lines identified genomic gains of 3q, 8q, 11q, 17q, and chromosome 20 in nine or more cell lines. CGH confirmed frequent loss of chromosome 18, 17p, 6q, and 8p. 14/15 cell lines demonstrated loss of chromosome 18q, either by loss of a copy of chromosome 18 (n = 5), all of 18q (n = 7) or portions of 18q (n = 2). Multicolor FISH (Spectral Karyotyping, or SKY) of 11 lines identified many complex structural chromosomal aberrations. 93 structurally abnormal chromosomes were evaluated, for which SKY added new information to 67. Several potentially site-specific recurrent rearrangements were observed. Chromosome region 18q11.2 was recurrently involved in nine cell lines, including formation of derivative chromosomes 18 from a t(18;22) (three cell lines), t(17;18) (two cell lines), and t(12;18), t(15;18), t(18;20), and ins(6;18) (one cell line each). To further define the breakpoints involved on chromosome 18, YACs from the 18q11.2 region, spanning approximately 8 Mb, were used to perform targeted FISH analyses of these lines. We found significant heterogeneity in the breakpoints despite their G-band similarity, including multiple independent regions of loss proximal to the already identified loss of DPC4 at 18q21.
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- Adelaide J, Huang HE, Murati A, Alsop AE, Orsetti B, et al: A recurrent chromosome translocation breakpoint in breast and pancreatic cancer cell lines targets the neuregulin/NRG1 gene. Genes Chromosomes Cancer 37:333–345 (2003).
- Aguirre AJ, Brennan C, Bailey G, Sinha R, Feng B, et al: High-resolution characterization of the pancreatic adenocarcinoma genome. Proc Natl Acad Sci USA 101:9067–9072 (2004).
- Alsop AE, Teschendorff AE, Edwards PA: Distribution of breakpoints on chromosome 18 in breast, colorectal, and pancreatic carcinoma cell lines. Cancer Genet Cytogenet 164:97–109 (2006).
- Bardi G, Johansson B, Pandis N, Mandahl N, Bak-Jensen E, et al: Karyotypic abnormalities in tumours of the pancreas. Br J Cancer 67:1106–1112 (1993).
- Bashyam MD, Bair R, Kim YH, Wang P, Hernandez-Boussard T, et al: Array-based comparative genomic hybridization identifies localized DNA amplifications and homozygous deletions in pancreatic cancer. Neoplasia 7:556–562 (2005).
- Birnbaum D, Adelaide J, Popovici C, Charafe-Jauffret E, Mozziconacci MJ, Chaffanet M: Chromosome arm 8p and cancer: a fragile hypothesis. Lancet Oncol 4:639–642 (2003).
- Curtis LJ, Li Y, Gerbault-Seureau M, Kuick R, Dutrillaux AM, et al: Amplification of DNA sequences from chromosome 19q13.1 in human pancreatic cell lines. Genomics 53:42–55 (1998).
- Fukushige S, Waldman FM, Kimura M, Abe T, Furukawa T, et al: Frequent gain of copy number on the long arm of chromosome 20 in human pancreatic adenocarcinoma. Genes Chromosomes Cancer 19:161–169 (1997).
- Furukawa T, Sunamura M, Horii A: Molecular mechanisms of pancreatic carcinogenesis. Cancer Sci 97:1–7 (2006).
- Ghadimi BM, Schrock E, Walker RL, Wangsa D, Jauho A, et al: Specific chromosomal aberrations and amplification of the AIB1 nuclear receptor coactivator gene in pancreatic carcinomas. Am J Pathol 154:525–536 (1999).
- Griffin CA, Hruban RH, Long PP, Morsberger LA, Douna-Issa F, Yeo CJ: Chromosome abnormalities in pancreatic adenocarcinoma. Genes Chromosomes Cancer 9:93–100 (1994).
- Griffin CA, Hruban RH, Morsberger LA, Ellingham T, Long PP, et al: Consistent chromosome abnormalities in adenocarcinoma of the pancreas. Cancer Res 55:2394–2399 (1995).
- Gysin S, Rickert P, Kastury K, McMahon M: Analysis of genomic DNA alterations and mRNA expression patterns in a panel of human pancreatic cancer cell lines. Genes Chromosomes Cancer 44:37–51 (2005).
- Hahn SA, Hoque AT, Moskaluk CA, da Costa LT, Schutte M, et al: Homozygous deletion map at 18q21.1 in pancreatic cancer. Cancer Res 56:490–494 (1996).
- Harada T, Okita K, Shiraishi K, Kusano N, Furuya T, et al: Detection of genetic alterations in pancreatic cancers by comparative genomic hybridization coupled with tissue microdissection and degenerate oligonucleotide primed polymerase chain reaction. Oncology 62:251–258 (2002).
- Harada T, Okita K, Shiraishi K, Kusano N, Kondoh S, Sasaki K: Interglandular cytogenetic heterogeneity detected by comparative genomic hybridization in pancreatic cancer. Cancer Res 62:835–839 (2002).
- Heidenblad M, Schoenmakers EF, Jonson T, Gorunova L, Veltman JA, et al: Genome-wide array-based comparative genomic hybridization reveals multiple amplification targets and novel homozygous deletions in pancreatic carcinoma cell lines. Cancer Res 64:3052–3059 (2004).
- Hoglund M, Gorunova L, Jonson T, Dawiskiba S, Andren-Sandberg A, et al: Cytogenetic and FISH analyses of pancreatic carcinoma reveal breaks in 18q11 with consistent loss of 18q12–qter and frequent gain of 18p. Br J Cancer 77:1893–1899 (1998).
- Holzmann K, Kohlhammer H, Schwaenen C, Wessendorf S, Kestler HA, et al: Genomic DNA-chip hybridization reveals a higher incidence of genomic amplifications in pancreatic cancer than conventional comparative genomic hybridization and leads to the identification of novel candidate genes. Cancer Res 64:4428–4433 (2004).
ISCN (2005): An International System for Human Cytogenetic Nomenclature. Shaffer LG, Tommerup N (eds) (S Karger, Basel 2005).
- Jaffee EM, Schutte M, Gossett J, Morsberger LA, Adler AJ, et al: Development and characterization of a cytokine-secreting pancreatic adenocarcinoma vaccine from primary tumors for use in clinical trials. Cancer J Sci Am 4:194–203 (1998).
- Johansson B, Bardi G, Heim S, Mandahl N, Mertens F, et al: Nonrandom chromosomal rearrangements in pancreatic carcinomas. Cancer 69:1674–1681 (1992).
- Karhu R, Mahlamaki E, Kallioniemi A: Pancreatic adenocarcinoma – genetic portrait from chromosomes to microarrays. Genes Chromosomes Cancer 45:721–730 (2006).
- Kitoh H, Ryozawa S, Harada T, Kondoh S, Furuya T, et al: Comparative genomic hybridization analysis for pancreatic cancer specimens obtained by endoscopic ultrasonography-guided fine-needle aspiration. J Gastroenterol 40:511–517 (2005).
- Lefter LP, Furukawa T, Sunamura M, Duda DG, Takeda K, et al: Suppression of the tumorigenic phenotype by chromosome 18 transfer into pancreatic cancer cell lines. Genes Chromosomes Cancer 34:234–242 (2002).
- Mahlamaki EH, Hoglund M, Gorunova L, Karhu R, Dawiskiba S, et al: Comparative genomic hybridization reveals frequent gains of 20q, 8q, 11q, 12p, and 17q, and losses of 18q, 9p, and 15q in pancreatic cancer. Genes Chromosomes Cancer 20:383–391 (1997).
- Mahlamaki EH, Barlund M, Tanner M, Gorunova L, Hoglund M, et al: Frequent amplification of 8q24, 11q, 17q, and 20q-specific genes in pancreatic cancer. Genes Chromosomes Cancer 35:353–358 (2002).
- Mahlamaki EH, Kauraniemi P, Monni O, Wolf M, Hautaniemi S, Kallioniemi A: High-resolution genomic and expression profiling reveals 105 putative amplification target genes in pancreatic cancer. Neoplasia 6:432–439 (2004).
- Nowak NJ, Gaile D, Conroy JM, McQuaid D, Cowell J, et al: Genome-wide aberrations in pancreatic adenocarcinoma. Cancer Genet Cytogenet 61:36–50 (2005).
- Pole JC, Courtay-Cahen C, Garcia MJ, Blood KA, Cooke SL, et al: High-resolution analysis of chromosome rearrangements on 8p in breast, colon and pancreatic cancer reveals a complex pattern of loss, gain and translocation. Oncogene 25:5693-5706 (2006).
- Riopel MA, Spellerberg A, Griffin CA, Perlman EJ: Genetic analysis of ovarian germ cell tumors by comparative genomic hybridization. Cancer Res 58:3105–3110 (1998).
- Schleger C, Arens N, Zentgraf H, Bleyl U, Verbeke C: Identification of frequent chromosomal aberrations in ductal adenocarcinoma of the pancreas by comparative genomic hybridization (CGH). J Pathol 91:27–32 (2000).
- Shiraishi K, Okita K, Kusano N, Harada T, Kondoh S, et al: A comparison of DNA copy number changes detected by comparative genomic hybridization in malignancies of the liver, biliary tract and pancreas. Oncology 60:151–161 (2001).
- Sirivatanauksorn V, Sirivatanauksorn Y, Gorman PA, Davidson JM, Sheer D, et al: Non-random chromosomal rearrangements in pancreatic cancer cell lines identified by spectral karyotyping. Int J Cancer 91:350–358 (2001).
- Solinas-Toldo S, Wallrapp C, Muller-Pillasch F, Bentz M, Gress T, Lichter P: Mapping of chromosomal imbalances in pancreatic carcinoma by comparative genomic hybridization. Cancer Res 56:3803–3807 (1996).
- Sunamura M, Lefter LP, Duda DG, Morita R, Inoue H, et al: The role of chromosome 18 abnormalities in the progression of pancreatic adenocarcinoma. Pancreas 28:311–316 (2004).
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