Skip to main content

Advertisement

SpringerLink
Log in

Frequent allelic imbalance at the ATM locus in DNA multiploid colorectal carcinomas

  • Oncogenomics
  • Published:
Oncogene Submit manuscript

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, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4

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

    Google Scholar 

  • 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

Download references

Author information

Authors and Affiliations

  1. Division of Pathology, Central Clinical Laboratory School of Medicine, Iwate Medical University, 19-1, Morioka, 020-8505, Japan

    Tamotsu Sugai, Wataru Habano, Noriyuki Uesugi, Yu-Fei Jiao, Shin-ichi Nakamura & Toru Yoshida

  2. Department of Surgery I, School of Medicine, Iwate Medical University, 19-1, Morioka, 020-8505, Japan

    Toru Yoshida & Taro Higuchi

Authors
  1. Tamotsu Sugai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wataru Habano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Noriyuki Uesugi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu-Fei Jiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shin-ichi Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Toru Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Taro Higuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tamotsu Sugai.

Rights and permissions

Reprints 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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204731

  • Springer Nature Limited

Keywords

This article is cited by

Search

Navigation