KRAS mutations

Pao W, Wang TY, Riely GJ et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoSMed2005, 2 ell. 

Lievre A, Bachet JB, Le Corre D et al. KRAS mutation status is predictive of response to cetuximab therapy in eoloreetal cancer. Cancer Res 2006 66 3992-3995. 

Schubbert S, Zenker M, Rowe SL et al (2006) Germline KRAS mutations cause Noonan syndrome. Nat Genet 38 331—336... 

A variety of molecular techniques are available to detect point mutations at a specific hot spot (e.g., the KRAS mutation at codons 12 and 13 or the BRAF mutation at codon 600). These methods include realtime PCR amplification and post-PCR melting curve analysis, allele-specific PCR, direct DNA sequencing, pyrosequencing, and PCR-RFLP. o,31-37 q methods demonstrate reliable detection of point mutations, such as the KRAS mutation in colorectal cancer or the BRAF mutation in thyroid cancer. 

FIGURE 2.8 Detection of a KRAS mutation in a colon cancer sample using DNA sequencing. The electropherogram demonstrates a G T mutation in codon 1 2. 

Ogino S, Kawasaki T, Brahmandam M, et al. Sensitive sequencing method for KRAS mutation detection by Pyrosequencing. Mol Diagn. 2005 7 413-421. 

The molecular mutational profile of SPCC is not well understood, though it is presumed to be similar to other tobacco-induced squamous cell carcinomas. One recent study did not find any evidence of KRAS mutations,... 

KRAS mutations of codon 12 are negative predictors of lung adenocarcinoma response to EGFR TKI therapy and are an adverse prognostic factor. 7272 hER2 (3%) and BRAE (1%) mutations are rarely identified in lung adenocarcinomas but are mutually exclusive with EGFR mutations... 

Lievre A, Bachet JB, Boige V, et al. KRAS mutations as an inde-pendentprognosticfactorinpatientswithadvancedcolorectalcancer treated with cetuximab. / Clin Oncol. 2008 26 374-379. 

Among all human cancers, DAs have the highest frequency of KRAS alterations, the oncogene being constitutively activated in approximately 90% of DAs. 07,136-139,141-145 However, it is important to point out that KRAS mutations are seen even in earliest forms of neoplastic transformation (namely PanIN-lA) they are a common incidental finding in pancreas, as well as in patients with chronic pancreatitis lacking invasive carcinoma thus they are by no means specific for cancer. Other oncogenes that are found to be activated in pancreatic cancer include AIBl, BRAF, c-MYC, and... 

These neoplasms often have TP53 gene mutations, and immunolabeling for the p53 protein has been shown to label the pleomorphic mononuclear cells but not the osteoclast-like giant cells. Additionally, genetic analyses have demonstrated that the atypical mononuclear cells harbor KRAS mutations in about 90% of these... 

The majority of the cases show nuclear p53 staining and loss of DPC4 protein similar to the molecular signature found in DA. KRAS mutations are seen in the... 

By molecular/genetic analysis, KRAS mutations appear early and increase in frequency proportional to the degree of dysplasia. i 747-249 p53 overexpression appears to occur relatively late in in situ and invasive... 

SCA is virtually the only ductal tumor that does not show the pancreatic ductal differentiation markers (mucins, mucin-related oncoproteins, and KRAS mutation). 

By molecular/genetic analysis, ACCs rarely, if at all, show KRAS mutations °48i,283,285,286 stark contrast with ductal cancers. Recent work has identified a high frequency of allelic loss on chromosomes 4q, lip, and 16q. " 487,288 jjj addition, 25% of ACCs have mutations in the APC/ -catenin pathway, a pattern similar to... 

The most common genetic alteration identified to date is LOH of the highly imprinted region of chromosome lip near the WT2 gene locus.Additionally, alterations in the adenomatous polyposis coli (APC)/ -catenin pathway have been reported in 50% to 80% of pancreatoblastomas.Most often, these involve the p-catenin gene (CTNNBlj. ssooo u Uke DAs, TP53 and KRAS mutations have not been detected.334.299,30i,302... 

Massarelli E et al. KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. Clinical Cancer Research 2007 13 2890-2896. 

Schernhammer, E.S., Giovannuccci, E., Fuchs, C.S., and Ogino, S., 2008. A prospective study of dietary folate and vitamin B and colon cancer according to microsatellite instability and KRAS mutational status. Cancer Epidemiol Biomarkers Prev. 17 2895-2898. 

KRAS mutation and anti-EGFR Colon Selection of therapy... 

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