Abstract
DNA multiploidy may involve specific DNA ploidy states with respect to genetic alterations such as oncogenes, tumor suppressor gene mutation and microsatellite instability. To clarify the role of DNA multiploidy in colorectal cancer, we analysed allelic imbalance involving the ATM gene, localized to chromosome 11q22-23 and thought to be involved in genetic stability, in a series of multiploid colorectal carcinomas. In addition, p53 gene mutation (exons 5–8) and allelic imbalance at 11q24 loci distal to the ATM locus were also examined. The crypt isolation technique coupled with DNA cytometric sorting and polymerase chain reaction assay using 10 microsatellite markers tightly linked to the ATM gene were used to study ATM allelic imbalance in 55 colorectal carcinomas (15 diploid, 13 aneuploid, 27 multiploid). While allelic imbalance at the ATM locus was rarely observed in diploid and aneuploid carcinomas, multiploid carcinomas exhibited a high frequency of ATM allelic imbalance. In multiploid carcinoma samples, diploid subpopulations showed a smaller range of allelic imbalance at the loci tested compared to aneuploid subpopulations that demonstrated allelic imbalance over a relatively large region. Also, the frequency of AI at 11q24 showed a similar tendency to that at the ATM locus for each DNA ploidy state. An association between p53 gene mutation and ATM allelic imbalance in multiploid carcinoma was also observed. Our results suggest that ATM allelic imbalance and p53 gene mutations occur during the progression from diploid to aneuploid cell populations in multiploid colorectal carcinomas.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Baffa R, Negrini M, Schichman SA, Huebner K, Croce CM . 1995 Proc. Natl. Acad. Sci. USA 92: 4922–4926
Baysal BE, van Schothorst EM, Farr JE, Lames ER, Devilee P, Richard CW . 1997 Genomics 44: 214–221
Bethwaite PB, Koreth J, Herrington CS, McGee JO . 1995 Br. J. Cancer 71: 814–818
Canman CE, Lim DS . 1998 Oncogene 17: 3301–3308
Carder PJ, Cripps KJ, Morris R, Collins S, White S, Bird CC, Wyllie AH . 1995 Br. J. Cancer 71: 215–218
Carter SL, Negrini M, Baffa R, Gillum DR, Rosengerg AL, Schwartz GF, Croce CM . 1994 Cancer Res. 54: 6270–6274
Connolly KC, Gabra H, Millwater CJ, Taylor KJ, Rabiasz GJ, Watson JEV, Smith JF, Wyllie AH, Jodrell DI . 1999 Cancer Res. 59: 2806–2809
Davis M, Hitchcock A, Foulkes WD, Campbell IG . 1996 Cancer Res. 56: 741–744
Gustafson CE, Young J, Leggett B, Searle J, Chenevix-Trench G . 1994 Br. J. Cancer 70: 395–397
Japanese Society for Cancer of the Colon, Rectum . 1997 Japanese Classification of Colorectal Carcinoma First English Edition Kanehara Co., Tokyo pp 30–63
Keldysh PL, Dragani TA, Fleischman EW, Konstantinova LN, Perevoschikov AG, Pierotti MA, Porta GD, Kopnin BP . 1993 Genes, Chromosomes Cancer 6: 45–50
Lange E, Borresen A, Chen X, Chessa L, Chiplunkar S, Concannon P, Dandekar S, Berken S, Lange K, Liang T, McConville C, Polakow J, Porras O, Rotman G, Sanal O, Sheikhavandi S, Shiloh Y, Sobel E, Taylor M, Telatar M, Teraoka S, Tolun A, Udar N, Uhrhammer N, Vangaite L, Wang Z, Wapelhorst B, Wright J, Yang H, Yang L, Ziv Y, Gatti R . 1995 Am. J. Hum. Genet. 57: 112–116
Meyn MS . 1995 Cancer Res. 55: 5991–6001
Meyn MS . 1999 Clin. Genet. 55: 289–304
Monaco C, Negrini M, Sozzi G, Veronese ML, Vorechovsky I, Godwin AK, Croce CM . 1997 Genomics 46: 217–222
Nakamura S, Goto J, Kitayama M, Kino I . 1994 Gastroenterology 106: 100–107
Offerhous GJA, De Feyter EP, Cornelisse CJ, Tersmette KWF, Floyd J, Kern SE, Vogelstein B, Hamilton SR . 1992 Gastroenterology 102: 1612–1619
Rasio D, Negrini M, Croce CM . 1995 Cancer Res. 55: 6053–6057
Rasio D, Negrini M, Manenti G, Dragani TA, Croce CM . 1995 Cancer Res. 55: 3988–3991
Sanchez Y, Wong C, Thoma RS, Wu Z, Piwnica-Worms H, Elledge SJ . 1997 Science 277: 1497–1501
Sugai T, Habano W, Nakamura S, Sato H, Uesugi N, Orii S, Itoh C, Katoh R . 2000a Hum. Pathol. 31: 925–930
Sugai T, Habano W, Nakamura S, Sato H, Uesugi N, Takahashi H, Jao YF, Yoshida T, Itoh C . 2000b Int. J. Cancer 88: 614–619
Sugai T, Habano W, Nakamura S, Uesugi N, Sasou S, Itoh C . 2000c Arch. Pathol. Lab. Med. 124: 382–386
Sugai T, Habano W, Nakamura S, Yoshida T, Uesugi N, Sasou S, Itoh C, Katoh R . 2000d Pathol. Res. Pract. 196: 145–150
Takagi M, Delia D, Chessa L, Iwata S, Shigeta T, Kanke Y, Goi K, Asada M, Eguchi M, Kodama C, Mizutani S . 1998 Cancer Res. 58: 4923–4629
Turnbull RB, Kyle K, Watson FR, Spratt J . 1967 Ann. Surg. 166: 420–427
Uhrhammer N, Bay JO, Pernin D, Rio P, Grancho M, Kwiatkowski F, Gosse-Brun S, Daver A, Bignon YJ . 1999 Oncol. Rep. 6: 655–658
Vanagaite L, James MR, Rotman G, Savitsky K, Bar-Shira A, Gilad S, Ziv Y, Uchenik V, Sartiel A, Collins FS, Sheffield VC, Ritchard CV, Weissenbach J, Shiloh Y . 1995 Hum. Genet. 95: 451–454
Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AMM, Bos JL . 1988 New Engl. J. Med. 319: 525–532
Vogelstein B, Fearon ER, Kern SE, Hamilton SR, Preisinger AC, Nakamura Y, White R . 1989 Science 244: 207–211
Vorechovsky I, Juo L, Dyer MJS, Catovsky D, Amlot PL, Yaxley JC, Foroni L, Hammarstrom L, Webster ADB, Yuille MAR . 1997 Nature Genet. 17: 96–99
Xie G, Habbersett RC, Jia Y, Peterson SR, Lehnert BE, Bradbury EM, D Anna JA . 1998 Oncogene 16: 721–736
Zbieranowski I, Demianiuk C, Bell V, Knape WA, Murray D . 1993 Anal. Cell. Pathol. 5: 69–84
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sugai, T., Habano, W., Uesugi, N. et al. Frequent allelic imbalance at the ATM locus in DNA multiploid colorectal carcinomas. Oncogene 20, 6095–6101 (2001). https://doi.org/10.1038/sj.onc.1204731
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1204731
Keywords
This article is cited by
-
ATM and MET kinases are synthetic lethal with nongenotoxic activation of p53
Nature Chemical Biology (2012)
-
Atm is a negative regulator of intestinal neoplasia
Oncogene (2008)
-
Analysis of SMAD4/DPC4 gene alterations in multiploid colorectal carcinomas
Journal of Gastroenterology (2005)