title: Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population.
abstract: Activation of the phosphatidylinositol 3'-kinase (PI3K)/AKT pathway results in an increase in cell proliferation and survival. Somatic mutations within the PI3K catalytic subunit, PIK3CA are common cause of increasing PI3K activity and are believed to be oncogenic in many cancer types. Few reports addressed the association between PIK3CA mutations and tumor progression specifically in microsatellite instable (MSI) colorectal cancer (CRC). In the present study, we have evaluated PIK3CA mutational status in a series of 410 Middle Eastern CRC and 13 colon cell lines to study the prevalence of PIK3CA mutations in MSI cases, PTEN expression in CRC and possibility of therapeutic targeting of this set of patients. PIK3CA mutations were found in four of the cell lines tested and 51 colorectal carcinomas (12.2%). Three of these four mutated cell lines were MSI. PTEN was inactivated in 66.1% of the CRC. Furthermore, we observed a strong association between PIK3CA mutations and MSI status (P=0.0046) while PTEN loss was more frequent in microsatellite stable (MSS) CRC (P=0.043). A high prevalence of genetic alterations in PI3K/AKT pathway in Saudi cohort of CRC, predominance of PIK3CA mutations in the MSI subgroup and their possible involvement in development/progression of this subset of CRC are some of the significant findings of our study.
authors.affiliation: Department of Human Cancer Genomic Research, King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia.
authors.forename: J
authors.initials: J
authors.lastname: Abubaker
authors.forename: P
authors.initials: P
authors.lastname: Bavi
authors.forename: S
authors.initials: S
authors.lastname: Al-Harbi
authors.forename: M
authors.initials: M
authors.lastname: Ibrahim
authors.forename: A K
authors.initials: AK
authors.lastname: Siraj
authors.forename: N
authors.initials: N
authors.lastname: Al-Sanea
authors.forename: A
authors.initials: A
authors.lastname: Abduljabbar
authors.forename: L H
authors.initials: LH
authors.lastname: Ashari
authors.forename: S
authors.initials: S
authors.lastname: Alhomoud
authors.forename: F
authors.initials: F
authors.lastname: Al-Dayel
authors.forename: S
authors.initials: S
authors.lastname: Uddin
authors.forename: K S
authors.initials: KS
authors.lastname: Al-Kuraya
mesh_terms: D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000208:ethnology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D020869:Gene Expression Profiling; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D012529:Saudi Arabia; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human