title: Mutational analysis of PI3K/AKT and RAS/RAF pathway activation in malignant salivary gland tumours with a new mutation of PIK3CA.
abstract: The phosphoinositide 3-kinase (PIK3)/v-akt murine thymoma (AKT) oncogene pathway and the RAS/RAF pathway are involved in regulating the signalling of multiple biological processes, including apoptosis, metabolism, cell proliferation, and cell growth. Mutations in the genes within these pathways are frequently found in several tumours. The aim of this study was to investigate the frequency of mutations in the PIK3CA, BRAF, and KRAS genes in cases of malignant salivary gland tumours. Mutational analysis of the PIK3CA, KRAS, and BRAF genes was performed by direct sequencing of material from 21 patients with malignant salivary gland tumours who underwent surgery between 1992 and 2001. No mutations were found in the KRAS exon 2, BRAF exon 15, or PIK3CA exon 9 genes. However, an unpublished mutation of the PIK3CA gene in exon 20 (W1051 stop mutation) was found in one case of adenocarcinoma NOS. The impact of this mutation on the biological behaviour of the tumour has yet to be explored, however the patient with adenocarcinoma NOS harbouring this mutation has survived for over 20 years following surgery despite a high stage at presentation. Further studies with more homogeneous patient cohorts are needed to address whether this mutation reflects a different clinical presentation and may benefit from targeted treatment strategies.
authors.affiliation: Institute of Pathology, The Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Shalmon
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, The Chaim Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Drendel
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, The Chaim Sheba Medical Center, Tel Hashomer, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Wolf
authors.affiliation: Cancer Research Center, The Chaim Sheba Medical Center, Tel-Hashomer, Israel; Department of Oral Pathology and Oral Medicine, The Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: hirshmd@post.tau.ac.il.
authors.forename: A
authors.initials: A
authors.lastname: Hirshberg
authors.affiliation: Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Cancer Research Center, The Chaim Sheba Medical Center, Tel-Hashomer, Israel; Department of Obstetrics and Gynecology, Chaim Sheba Medical Center (Tel Hashomer), Ramat Gan, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Cohen
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000378:metabolism*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051057:Proto-Oncogene Proteins c-akt; D019908:Proto-Oncogene Proteins c-raf; D016283:Proto-Oncogene Proteins p21(ras)
keywords: AKT; PI3K; RAS; head and neck cancer; salivary gland cancer