Challenging a dogma: co-mutations exist in MAPK pathway genes in colorectal cancer.
Sequencing of genes encoding mitogen-activated protein kinase (MAPK) pathway proteins in colorectal cancer (CRC) has established as dogma that of the genes in a pathway only a single one is ever mutated. We searched for cases with a mutation in more than one MAPK pathway gene (co-mutations). Tumor t...
| Publicado en: | Virchows Archiv: European Journal of Pathology Vol. 469; no. 4; pp. 459 - 465 |
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| Autores principales: | , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Oct2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=118280619&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 118280619 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 09456317 O1Z jtl: Virchows Archiv: European Journal of Pathology issn: 09456317 maglogo: N pubinfo: dt: Oct2016 vid: 469 iid: 4 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 118280619 118280619 NLM27401719 10.1007/s00428-016-1991-0 NLM27401719 118280619 ppf: 459 ppct: 6 formats: fmt: @attributes: type: P tig: atl: Challenging a dogma: co-mutations exist in MAPK pathway genes in colorectal cancer. aug: au: Grellety, Thomas Gros, Audrey Pedeutour, Florence Merlio, Jean-Philippe Duranton-Tanneur, Valerie Italiano, Antoine Soubeyran, Isabelle affil: Department of Medical Oncology , Institut Bergonié , 229 Cours de L'Argonne 33076 Bordeaux France sug: subj: Signal Transduction Colorectal Neoplasms Colorectal Neoplasms Pathology Phosphotransferases Membrane Proteins Retrospective Design Aged Aged, 80 and Over Female Male Middle Age Transferases Hydrolases Proteins Colorectal Neoplasms Diagnosis Adult Sequence Analysis Scales Aged: 65+ years Aged, 80 & over Middle Aged: 45-64 years Adult: 19-44 years Female Male ab: Sequencing of genes encoding mitogen-activated protein kinase (MAPK) pathway proteins in colorectal cancer (CRC) has established as dogma that of the genes in a pathway only a single one is ever mutated. We searched for cases with a mutation in more than one MAPK pathway gene (co-mutations). Tumor tissue samples of all patients presenting with CRC, and referred between 01/01/2008 and 01/06/2015 to three French cancer centers for determination of mutation status of RAS/RAF+/-PIK3CA, were retrospectively screened for co-mutations using Sanger sequencing or next-generation sequencing. We found that of 1791 colorectal patients with mutations in the MAPK pathway, 20 had a co-mutation, 8 of KRAS/NRAS, and some even with a third mutation. More than half of the mutations were in codons 12 and 13. We also found 3 cases with a co-mutation of NRAS/BRAF and 9 with a co-mutation of KRAS/BRAF. In 2 patients with a co-mutation of KRAS/NRAS, the co-mutation existed in the primary as well as in a metastasis, which suggests that co-mutations occur early during carcinogenesis and are maintained when a tumor disseminates. We conclude that co-mutations exist in the MAPK genes but with low frequency and as yet with unknown outcome implications. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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