title: Frequent PIK3CA gene amplification and its clinical significance in colorectal cancer.
abstract: Using a DNA microarray approach to screen for gene copy number changes in 20 colorectal (CR) carcinoma samples and filtering for high-level DNA copy number changes, we detected an amplicon at 3q26 containing the PIK3CA gene. Fluorescence in situ hybridization was employed for evaluation of PIK3CA amplification on a progression CR tissue microarray containing 448 CR carcinomas, normal mucosa, and adenomas with follow-up information. PIK3CA amplification (ratio PIK3CA/centromere 3 > or = 2.0) was found in 38% of cancers, while another 19% of tumours had PIK3CA gains (ratio >1.0 but <2.0). Both PIK3CA amplification and gains were associated with high levels of PIK3CA protein expression and no association was seen between PIK3CA amplification and PIK3CA mutation. In a subset of 220 patients who received adjuvant chemotherapy and/or radiotherapy, survival in patients with PIK3CA-amplified cancers was significantly longer compared with patients with cancers without amplification. This association was independent of stage, grade, histology subtype, gender, and age categories. Interestingly, PIK3CA amplification was also seen in CR adenomas, indicating an early genetic alteration, and was also a frequent event in colorectal carcinogenesis. Furthermore, PIK3CA amplification is an independent prognostic marker for better survival and may be one of the promising markers to define CRC subsets that may maximally benefit from adjuvant therapy.
authors.affiliation: Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Zeenath
authors.initials: Z
authors.lastname: Jehan
authors.forename: Prashant
authors.initials: P
authors.lastname: Bavi
authors.forename: Mehar
authors.initials: M
authors.lastname: Sultana
authors.forename: Jehad
authors.initials: J
authors.lastname: Abubaker
authors.forename: Rong
authors.initials: R
authors.lastname: Bu
authors.forename: Azhar
authors.initials: A
authors.lastname: Hussain
authors.forename: Ghazi
authors.initials: G
authors.lastname: Alsbeih
authors.forename: Nasser
authors.initials: N
authors.lastname: Al-Sanea
authors.forename: Alaa
authors.initials: A
authors.lastname: Abduljabbar
authors.forename: Luai H
authors.initials: LH
authors.lastname: Ashari
authors.forename: Samar
authors.initials: S
authors.lastname: Alhomoud
authors.forename: Fouad
authors.initials: F
authors.lastname: Al-Dayel
authors.forename: Shahab
authors.initials: S
authors.lastname: Uddin
authors.forename: Khawla S
authors.initials: KS
authors.lastname: Al-Kuraya
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D004812:Epidemiologic Methods; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human