New carcinoma genetics research from University of Thessaloniki, Department of Pathology discussed
2009 JUL 13 - (NewsRx.com) -- Research findings, 'Mutational analysis of the BRAF, RAS and EGFR genes in human adrenocortical carcinomas,' are discussed in a new report. According to recent research published in the journal Endocrine-related Cancer, "The serine/threonine kinase B-Raf plays a key role in the Ras/Raf/MEK/ERK pathway that relays extracellular signals for cell proliferation and survival. Several types of human malignancies harbor activating BRAF mutations, most frequently a V600E substitution." "The epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase (TK) receptor that mediates proliferation and survival signaling, is expressed in a wide variety of normal and neoplastic tissues. EGFR inhibitors have produced objective responses in patients with non-small cell lung carcinomas harboring activating EGFR TK domain somatic mutations. We evaluated the presence of mutations in BRAF (exons 11 and 15), KRAS (exons 1 and 2), NRAS (exons 1 and 2), and EGFR (exons 18-21) in adrenal carcinomas (35 tumor specimens and two cell lines) by DNA sequencing. BRAF mutations were found in two carcinomas (5.7%). Four carcinomas (11.4%) carried EGFR TK domain mutations. One specimen carried a KRAS mutation, and another carried two NRAS mutations. No mutations were found in the two adrenocortical cell lines. BRAF-and EGFR-mutant tumor specimens exhibited stronger immunostaining for the phosphorylated forms of the MEK and ERK kinases than their wild-type counterparts. EGFR-mutant carcinomas exhibited increased phosphorylation of EGFR (Tyr 992) compared with wild-type carcinomas. We conclude that BRAF, RAS, and EGFR mutations occur in a subset of human adrenocortical carcinomas," wrote V. Kotoula and colleagues, University of Thessaloniki, Department of Pathology. The researchers concluded: "Inhibitors of the Ras/Raf/MEK/ERK and EGFR pathways represent candidate targeted therapies for future clinical trials in carefully selected patients with adrenocortical carcinomas harboring respective activating mutations." Kotoula and colleagues published their study in Endocrine-related Cancer (Mutational analysis of the BRAF, RAS and EGFR genes in human adrenocortical carcinomas. Endocrine-related Cancer, 2009;16(2):565-72). For additional information, contact V. Kotoula, Aristotle University of Thessaloniki, Dept. of Pathology, School of Medicine, University Campus, Thessaloniki 54006, Greece. The publisher's contact information for the journal Endocrine-related Cancer is: Springer, 233 Spring Street, New York, NY 10013, USA. Keywords: Greece, Thessaloniki, Carcinoma Genetics, Adrenal Cancer, Adrenal Carcinoma, Adrenocortical Cancer, Adrenocortical Carcinoma, Cell Proliferation, DNA Research, DNA Sequence Proteomics, Deoxyribonucleic Acid, Endocrine-Related Cancer, Enzyme Research, Kinase, Lung Cancer, Lung Carcinoma, Oncology, Pathology, Proteins, Small Cell Carcinoma, Tyrosine Kinase. This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2009, Clinical Oncology Week via NewsRx.com.
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