KRAS insertions in colorectal cancer: What do we know about unusual KRAS mutations?

Author(s)

de Macedo, Mariana Petaccia ^[1] ; Cernaglia Aureliano de Lima, Luiz Guilherme ^[1] ; Ferreira de Souza Begnami, Maria Dirlei ^[1] ; de Melo, Fernanda Machado ^[1] ; Brot Andrade, Louise D. ^[1] ; Garcia Lisboa, Bianca Cristina ^[1] ; Soares, Luisa Martelli ^[2] ; Soares, Fernando Augusto ^[1] ; Carraro, Dirce Maria ; da Cunha, Isabela Werneck ^[1]

Affiliation

^[1] AC Camargo Canc Ctr, Dept Anat Pathol, Dept Mol Diag, BR-01509010 Sao Paulo - Brazil

^[2] UNESP, Sch Vet Med, Botucatu, SP - Brazil

• Document type: Journal article
• Source: Experimental and Molecular Pathology; v. 96, n. 2, p. 257-260, APR 2014.
• Web of Science Citations: 8

Abstract

Introduction: KRAS mutations are negative predictors of the response to anti-EGFR therapy in colorectal carcinomas (CRCs). Point mutations in codons 12,13, and 61 are the most common KRAS mutations in CRC There are few reports on insertions in KRAS, and little is known about its ability to activate the RAS pathway. The scarcity of data regarding insertion frequencies and nucleotide additions in KRAS impedes the management of patients with such mutations. We present data on KRAS insertions in CRC and discuss a case. Materials and methods: Pyrosequencing and Sanger sequencing were performed to identify KRAS and BRAF mutations in paraffin-embedded samples of CRC Expression of mismatch repair proteins was examined by immunohistochemistry. Results: We detected a GGT insertion between codons 12 and 13 (c.36\_37insGGT;p.G12\_G13insG) in a CRC patient. We found that insertions in KRAS is very rare in CRC and that the most frequent type of insertion is c36\_37insGGT. Conclusions: KRAS gene insertions represent a diagnostic and clinical challenge due to the difficult and unusual pyrosequencing findings and the lack of information regarding its clinical impact. (C) 2014 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 11/08510-2 - Mutational status of the Kras gene in primary and metastatic colorectal carcinomas
• Grantee: Isabela Werneck da Cunha
• Support Opportunities: Regular Research Grants