RAS signaling in colorectal carcinomas through alterations of RAS, RAF, NF1, and/or RASSF1A

Terje Ahlquist, Irene Bottillo, Stine A. Danielsen, Gunn I. Meling, Torleiv O. Rognum, Guro E. Lind, Bruno Dallapiccola, Ragnhild A. Lothe

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

More than half of all colorectal carcinomas are known to exhibit an activated mitogen-activated protein kinase pathway. The NF1 gene, a negative regulator of KRAS, has not previously been examined in a series of colorectal cancer. In the present study, primary colorectal carcinomas stratified according to microsatellite instability status were analyzed. The whole coding region of NF1 was analyzed for mutations using denaturing high-performance liquid chromatography and sequencing, and the copy number alterations of NF1 were examined using multiple ligation-dependent probe amplification and real-time polymerase chain reaction. The mutational hot spots in KRAS and BRAF were sequenced, and promoter hypermethylation status of RASSF1A was assessed with a methylation-specific polymerase chain reaction. One sample had two missense mutations in NF1, whereas nine additional tumors had intronic mutations likely to affect exon splicing. Interestingly, 8 of these 10 tumors were microsatellite-unstable. Four other tumors showed a duplication of NF1. Mutations in KRAS and BRAF were mutually exclusive and were present at 40% and 22%, respectively. RASSF1A was hypermethylated in 31% of the samples. We show that the RAS signaling network is extensively dysregulated in colorectal carcinomas, because more than 70% of the tumors had an alteration in one or more of the four examined components.

Original languageEnglish
Pages (from-to)680-686
Number of pages7
JournalNeoplasia (United States)
Volume10
Issue number7
DOIs
Publication statusPublished - Jul 2008

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Colorectal Neoplasms
Mutation
Neoplasms
Microsatellite Instability
Missense Mutation
Mitogen-Activated Protein Kinases
Microsatellite Repeats
Methylation
Ligation
Real-Time Polymerase Chain Reaction
Exons
High Pressure Liquid Chromatography
Polymerase Chain Reaction
Genes

ASJC Scopus subject areas

  • Cancer Research

Cite this

Ahlquist, T., Bottillo, I., Danielsen, S. A., Meling, G. I., Rognum, T. O., Lind, G. E., ... Lothe, R. A. (2008). RAS signaling in colorectal carcinomas through alterations of RAS, RAF, NF1, and/or RASSF1A. Neoplasia (United States), 10(7), 680-686. https://doi.org/10.1593/neo.08312

RAS signaling in colorectal carcinomas through alterations of RAS, RAF, NF1, and/or RASSF1A. / Ahlquist, Terje; Bottillo, Irene; Danielsen, Stine A.; Meling, Gunn I.; Rognum, Torleiv O.; Lind, Guro E.; Dallapiccola, Bruno; Lothe, Ragnhild A.

In: Neoplasia (United States), Vol. 10, No. 7, 07.2008, p. 680-686.

Research output: Contribution to journalArticle

Ahlquist, T, Bottillo, I, Danielsen, SA, Meling, GI, Rognum, TO, Lind, GE, Dallapiccola, B & Lothe, RA 2008, 'RAS signaling in colorectal carcinomas through alterations of RAS, RAF, NF1, and/or RASSF1A', Neoplasia (United States), vol. 10, no. 7, pp. 680-686. https://doi.org/10.1593/neo.08312
Ahlquist T, Bottillo I, Danielsen SA, Meling GI, Rognum TO, Lind GE et al. RAS signaling in colorectal carcinomas through alterations of RAS, RAF, NF1, and/or RASSF1A. Neoplasia (United States). 2008 Jul;10(7):680-686. https://doi.org/10.1593/neo.08312
Ahlquist, Terje ; Bottillo, Irene ; Danielsen, Stine A. ; Meling, Gunn I. ; Rognum, Torleiv O. ; Lind, Guro E. ; Dallapiccola, Bruno ; Lothe, Ragnhild A. / RAS signaling in colorectal carcinomas through alterations of RAS, RAF, NF1, and/or RASSF1A. In: Neoplasia (United States). 2008 ; Vol. 10, No. 7. pp. 680-686.
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