Abstract 3799: PIK3CA and BRAF mutational status and association with clinicopathological features in Iranian colonrectal cancer patients
Authors: Ghaffarpour Massoud , Pargoo Esmaeel Mohammadi , Sobhani Sanaz , Pirmoradi Saeid , Hosseini Zahra Mostakhdemin , Kamali Fatemeh , Fereidooni Forouzandeh , Houshmand Massoud 
Published: June 2012

Abstract
Introduction:Colorectal cancer (CRC) is one of the most important malignancies worldwide and it is the third most common cancer amongst Males and the fourth amongst females in Iranian cancer patients. Somatic mutations of PIK3CA were described in CRCs with a frequency ranging from 13.6% to 32%.In CRCs, 3 mutational hot spots were described (E542K, E545K, and H1047R), covering about 80% of all PIK3CA mutations. Mutations of the B-RAF have been identified in colorectal cancer with a ranging from 5% to 22 %.in CRC, All of the mutations of B-RAF have been found in exons 11 and 15, which encode the kinase domain of this protein.V600E substitution in exon 15 covering about 90% of all B-raf mutations.The aim of this study was to identify PIK3CA gene mutations in exons 9 and 20 and B-Raf gene mutations in exon 11 and 15 among Iranian CRC patients, and to consider whether they are linked with the clinicopathological parameters. Materials and Methods: Patients and tissue specimens; Tissue samples were obtained from 27 consecutive patients with CRC (10 men and 17 women; age range, 32-88 years; with median age of 61.3 years). Histopathological examinations were performed, and all tumors were confirmed as adenocarcinoma.Mutational analysis of PIK3CA in tumor samples: Fresh tumors, containing at least 70% of neoplastic cells and their adjacents were extracted for genomic DNA using the QIAamp Mini kit (Qiagen in accordance with the manufacturer 'sinstructions. We searched for PIK3CA mutations in exons 9 and 20.PIK3CA exon 9 includes codons 542 and 545, PIK3CA exon 20 and B-Raf mutations in exons 11 and 15 where the large majority of mutations occur in these genes. The PI3KCA and B-Raf mutational analyses were made by means of PCR sequencing. Results and conclusion: 21 (77.77%) patients had adenocarcinomas and 6 (22.23%) had mucinous adenocarcinomas. patients had stage I, II and III or IV disease with14.76%, 44.44%and 40.8% respectively and histological grade I, II and III with 66.6%,25.92% and 7.4%. respectively. Among the 27 samples analyzed (21were primary tumors and 6were metastases). The frequency of mutations in PIK3CA were present in 11.1% (3 of27) of the samples (11.1% mutation in exon 9(c.1633G&gt;A E545K and no mutation in exon 20). The frequency of mutation in B-Raf were present in 3.7%(1 of 27) of the samples(3.7% mutation in exon 15;V600E and no mutation in exon 9).The presence of PIK3CA and B-Raf mutation were not a significance associated with gender, histological grade, age, or cancer stage in patients with adenocarcinoma of the CRC(P&gt;0.05).Although many study have been shown in CRCs, 3 mutational hot spots for PIK3CA (E542K, E545K, and H1047R) and 2 mutational hot spots for B-RAf, our study indicated mutations were just in exon 9(E542K) and exon 15(V600E) and more samples should be investigate in exon 9,20 and other exons of PIK3CA gene and exons of B-RAF gene among Iranian colorectal cancer patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3799. doi:10.1158/1538-7445.AM2011-3799