Abstract
Colorectal cancer (CRC) is a leading cause of cancer death and the mechanism for variable outcome in this disease is not yet fully understood. It is hypothesized that differences in the genetic make-up of tumours may be partially responsible for the differences observed in survival among same staged individuals for this disease. In this study the tumour genomes of 29 consecutive patients undergoing surgery for Dukes’ C CRC were assessed by comparative genomic hybridization (CGH). In addition, the CGH profiles from the tumours were compared with those from eight colorectal cell lines. Great variation in genetic grade (all detectable aberrations i.e., loss + gain) was observed in 29 Dukes’ C colorectal tumours by CGH (median four aberrations per tumour, range 0–20). Gain was found in 76% and loss in 41% of tumours. The most frequently observed regions of gain were 13q (27.6%), 20q (27.6%), 7p (24.1%), 8q (24.1%), and 1q (20.7%) and loss were 18q (31%), 4q (20.7%), 17p (20.7%), 18p (20.7%), and 15q (20.1%). None of these specific genomic aberrations were associated with patient survival. However, patients with more than two aberrations had a better survival than patients with fewer regions of loss and gain (P = 0.02). CRC cell lines had similar regions of loss or gain as the tumours. However, the frequency of genomic aberrations was much greater in the CRC cell lines. Although genomic change in CRC is relevant to the survival of patients with Dukes’ C CRC, careful analysis is required to identify cell lines which are representative models of CRC genomics. © 2001 Cancer Research Campaign http://www.bjcancer.com
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References
Al-Mulla F, Keith NW, Pickford IR, Going J and Birnie GD (1999) Comparative genomic hybridisation analysis of primary colorectal carcinomas and their synchronous metastases. Gene Chromosome Cancer 24: 306–314
Barth TFE, Benner A, Bentz M, Döhner H, Möller P and Lichter P (2000) Risk of false positive results in comparative genomic hybridisation. Gene Chromosome. Cancer 28: 353–357
Boring CC, Squires TS and Tong T (1993) Cancer Statistics. Cancer J Clin 43: 7–10
Cahill DP, Lengauer C, Yu J, Riggins GJ, Wilson JK, Markowitz SD, Kinzler KW and Vogelstein B (1998) Mutations of mitotic checkpoint genes in human cancers. Nature 392: 300–303
Cahill DP, Kinzler KW, Vogelstein B and Lengauer C (1999) Genetic instability and Darwinian selection in tumours. Trends Cell Biol 9: M57–60
Collins C, Rommens JM, Kowbel D, Godfrey T, Tanner M, Hwang S, Polikoff D, Nonet G, Cochran J, Myambo K, Jay KE, Froula J, Cloutier T, Kuo WL, Yaswen P, Dairkee S, Giovanola J, Huechison BG, Isola J, Kallioniemi OP, Palazzolo M, Martin C, Ericsson C, Pinkel D, Albertson D, Li WB and Gray JW (1998) Positional cloning of ZNF217 and NABC1: Genes amplified at 20q13.2 and overexpressed in breast carcinoma. Proc Natl Acad Sci USA 95: 8703–8708
De Angelis PM, Clausen OPF, Schjolberg A and Stokke T (1999) Chromosomal gains and losses in primary colorectal carcinomas detected by CGH and their associations with tumour DNA ploidy, genotypes and phenotypes. Br J Cancer 80: 526–535
Fearon ER and Vogelstein B (1990) A genetic model for colorectal tumourigenesis. Cell 61: 759–767
Georgiades JB, Curtis LJ, Morris RM, Bird CC and Wyllie AH (1999) Heterogeneity studies identify a subset of sporadic cancers without evidence for chromosomal or microsatellite instability. Oncogene 18: 7933–7940
Gryfe R, Kim H, Hsieh ET, Aronson MD, Holowaty EJ, Bull SB, Redston M and Gallinger S (2000) Tumour microsatellite instability and clinical outcome in young patients. N Engl J Med 42: 69–77
Hawkins NJ, Tomlinson I, Meagher A and Ward RL (2001) Microsatellite-stable diploid carcinoma: in a biologically distinct and aggressive subset of sporadic colorectal cancer. Br J Cancer 84: 232–236
Jones C, Payne J, Wells D, Delhanty JDA, Lakhani SR and Kortenkamp A (2000) Comparative genomic hybridization reveals extensive variation among different MCF-7 cell stocks. Cancer Genet Cytogen 117: 153–158
Kallioniemi A, Kallioniemi OP, Piper J, Tanner M, Stokke T, Chen L, Smith HS, Pinkel D, Gray JW and Waldman FM (1994) Detection and mapping of amplified DNA-sequences in breast-cancer by comparative genomic hybridization. Proc Natl Acad Sci USA 91: 2156–2160
Kallioniemi A, Kallioniemi O-P, Sudar D, Rutovitz D, Gray JW, Waldman F and Pinkel D (1992) Comparative genomic hybridisation for the genetic analysis of solid tumours. Science 258: 818–821
McLeod HL and Murray GI (1999) Tumour markers of prognosis in colorectal cancer. Br J Cancer 79: 191–203
Moertel CG, Fleming TR, MacDonald JS, Haller DG, Laurie JA, Tangen CM, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH and Mailliard JA (1995) Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage-III colon-carcinoma. Ann Intern Med 122: 321–326
Pisani P, Parkin MD, Bray F and Ferlay J (1999) Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer 83: 18–29
Reid T, Knutzen R, Steinbeck R, Blegen H, Schröck E, Heselmeyer K, du Manoir S and Auer G (1996) Comparative genomic hybridisation reveals a specific pattern of chromosomal gains and losses during the genesis of colorectal tumours. Gene Chromosome Cancer 15: 234–245
Reiss M, Gambavitalo C and Sartorelli AC (1986) Induction of tumor-cell differentiation as a therapeutic approach-preclinical models for hematopoietic and solid neoplasms. Cancer Treat Rep 70: 201–218
Rooney PH, Stevenson DAJ, Marsh S, Johnston PG, Haites NE, Cassidy J and McLeod HL (1998) CGH analysis of chromosomal alterations induced by the development of resistance to TS inhibitors. Cancer Res 58: 5042–5045
Rooney PH, Murray GI, Stevenson DAJ, Haites NE, Cassidy J and McLeod HL (1999) Comparative genomic hybridisation and chromosomal instability in solid tumours. Br J Cancer 80: 862–873
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Rooney, P., Boonsong, A., McKay, J. et al. Colorectal cancer genomics: evidence for multiple genotypes which influence survival. Br J Cancer 85, 1492–1498 (2001). https://doi.org/10.1054/bjoc.2001.2095
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DOI: https://doi.org/10.1054/bjoc.2001.2095
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