Linked Life Data

19190079

Source:http://linkedlifedata.com/resource/pubmed/id/19190079

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-5-29
pubmed:abstractText
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. 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1351-0088
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
565-72
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19190079-Adolescent, pubmed-meshheading:19190079-Adrenocortical Carcinoma, pubmed-meshheading:19190079-Adult, pubmed-meshheading:19190079-Aged, pubmed-meshheading:19190079-Aged, 80 and over, pubmed-meshheading:19190079-Child, pubmed-meshheading:19190079-Female, pubmed-meshheading:19190079-Genes, ras, pubmed-meshheading:19190079-Humans, pubmed-meshheading:19190079-Immunoenzyme Techniques, pubmed-meshheading:19190079-Male, pubmed-meshheading:19190079-Middle Aged, pubmed-meshheading:19190079-Mutation, pubmed-meshheading:19190079-Phosphorylation, pubmed-meshheading:19190079-Proto-Oncogene Proteins, pubmed-meshheading:19190079-Proto-Oncogene Proteins B-raf, pubmed-meshheading:19190079-Receptor, Epidermal Growth Factor, pubmed-meshheading:19190079-Retrospective Studies, pubmed-meshheading:19190079-Young Adult, pubmed-meshheading:19190079-ras Proteins
pubmed:year
2009
pubmed:articleTitle
Mutational analysis of the BRAF, RAS and EGFR genes in human adrenocortical carcinomas.
pubmed:affiliation
Department of Pathology, School of Medicine, Aristotle University of Thessaloniki, University Campus, Thessaloniki 54006, Greece. vkotoula@auth.gr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't