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Novel mutations of the suppressor gene PTEN in colorectal carcinomas stratified by microsatellite instability‐ and TP53 mutation‐ status
Author(s) -
Danielsen Stine A.,
Lind Guro E.,
Bjørnslett Merete,
Meling Gunn I.,
Rognum Torleiv O.,
Heim Sverre,
Lothe Ragnhild A.
Publication year - 2008
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20860
Subject(s) - pten , biology , microsatellite instability , cancer research , exon , mutation , colorectal cancer , coding region , intron , tumor suppressor gene , gene , genetics , cancer , microsatellite , carcinogenesis , signal transduction , allele , pi3k/akt/mtor pathway
PTEN regulates cell homeostasis by inhibiting growth signals transduced through PI3‐kinases. The gene is mutated in several cancer types, but so far, only a limited number of mutations have been reported in colorectal cancer. In the present study, direct sequencing was used to analyze the whole coding region and exon‐intron boundaries of PTEN in a series of microsatellite stable (n=34) and microsatellite unstable (n=30) colorectal carcinomas with known TP53 mutation status. We detected 21 PTEN mutations in altogether 13 tumors (20%), including 19 mutations in the coding sequence and two in the exon‐intron boundaries. Sixteen of these alterations have not been previously reported in colorectal cancer. Furthermore, seven out of the 13 altered tumors harbored more than one mutation, potentially leading to loss of gene function. Finally, all PTEN mutations found were in tumors harboring wild‐type TP53 . In conclusion, PTEN is mutated in a significant subgroup of colorectal carcinomas, and our findings further extend the previously small spectrum of reported PTEN changes. Additionally, it seems that mutations in PTEN and TP53 are mutually exclusive for this cancer type. © 2008 Wiley‐Liss, Inc.