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Alterations of the PPP2R1B gene located at 11q23 in human colorectal cancers
  1. Y Takagi,
  2. M Futamura,
  3. K Yamaguchi,
  4. S Aoki,
  5. T Takahashi,
  6. S Saji
  1. Second Department of Surgery, Gifu University School of Medicine, Tsukasa-machi, Gifu 500–8705, Japan
  1. Dr Y Takagi. Email: yutakagi{at}emailmsn.com

Abstract

BACKGROUND/AIMS In 1998 the PPP2R1B gene encoding the A subunit of the serine/threonine protein phosphatase was identified as a putative tumour suppressor gene in lung and colon cancer in the chromosome region 11q22–24. The aim of the present study was to determine the type of alterations in primary rectal cancers as well as colon cancers and the correlation between these alterations and clinicopathological data.

METHODS Mutation analyses of the PPP2R1B gene sequence encoding the binding sites of the catalytic C subunit (Huntington elongation A subunit TOR (HEAT) repeats 11–15) and partial binding sites of the regulatory B subunit were carried out on cDNA samples from 30 primary colorectal cancer specimens and corresponding normal tissues using a combination of the polymerase chain reaction and subsequent direct DNA sequencing.

RESULTS Five missense mutations producing amino acid substitutions were detected in the four colon cancer cases (13.3%; four of 30 colorectal cancers): 15glycine (GGT) to alanine (GCT) and 499leucine (TTA) to isoleucine (ATA) in the same case, and 498valine (GTG) to glutamic acid (GAG),500valine (GTA) to glycine (GGA), and 365serine (TCT) to proline (CCT). Of these five mutations, three (60%) were located in HEAT repeat 13 and four (80%) showed T to other nucleotide substitutions. In addition, a normal polymorphism,478leucine, was found. No correlation was found between these mutations and clinicopathological data.

CONCLUSION Our results suggest that the PPP2R1B gene is one of the true targets at 11q23, and its inactivation is involved in the development of all types of colorectal cancers.

  • PPP2R1B gene
  • colorectal cancer
  • tumour suppressor gene
  • protein phosphatase
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Footnotes

  • Abbreviations used in this paper:
    LOH
    loss of heterozygosity
    RT
    reverse transcriptase
    PCR
    polymerase chain reaction
    HEAT
    Huntington elongation A subunit TOR
    Ala
    alanine
    Val
    valine
    Gly
    glycine
    Glu
    glutamic acid
    Ile
    isoleucine
    Leu
    leucine
    Ser
    serine
    Pro
    proline
    PP2A
    protein phosphatase 2A

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