Alterations of the PPP2R1B gene located at 11q23 in human colorectal cancers.
OBJECTIVE
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): (15)glycine (GGT) to alanine (GCT) and (499)leucine (TTA) to isoleucine (ATA) in the same case, and (498)valine (GTG) to glutamic acid (GAG), (500)valine (GTA) to glycine (GGA), and (365)serine (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, (478)leucine, was found. No correlation was found between these mutations and clinicopathological data.


CONCLUSIONS
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.
Takagi
Y
Y
Second Department of Surgery, Gifu University School of Medicine, Japan. yutakagi@email.msn.com
Futamura
M
M
Yamaguchi
K
K
Aoki
S
S
Takahashi
T
T
Saji
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002869:Chromosome Aberrations / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D018076:DNA, Complementary / Q000032:analysis*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics*; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
D018076:DNA, Complementary; D009363:Neoplasm Proteins; D010749:Phosphoprotein Phosphatases