We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Mutation of TP53 and alteration of p14(arf) expression in EGFR- and KRAS-mutated lung adenocarcinomas.
- Authors
Cortot, Alexis B; Younes, Mohamad; Martel-Planche, Ghislaine; Guibert, Benoit; Isaac, Sylvie; Souquet, Pierre-Jean; Commo, Frédéric; Girard, Philippe; Fouret, Pierre; Brambilla, Elisabeth; Hainaut, Pierre; Soria, Jean-Charles
- Abstract
<bold>Background: </bold>In lung adenocarcinoma, inactivation of the tumor suppressor p53 may abrogate a safeguard mechanism preventing the development of tumors with activating mutations in EGFR or KRAS. To assess this hypothesis, we analyzed TP53 mutations and downregulation of p14(arf), a negative regulator of p53 activated by oncogenic signals, in a retrospective series of 96 patients with primary adenocarcinoma of the lung.<bold>Patients and Methods: </bold>Mutations in TP53 (exons 4-9), KRAS (exon 1), and EGFR (exons 18-21) were identified by direct sequencing of DNA from formalin-fixed, paraffin-embedded resected tumors. Expression of p14(arf) was semiquantitatively evaluated by immunohistochemical analysis.<bold>Results: </bold>TP53, KRAS, and EGFR mutations were detected in 42 of 93 (45.2%), 15 of 95 (15.8%), and 31 of 90 (34.4%) cases, respectively. Low p14(arf) expression was observed in 19 of 91 cases (20.9%). Disruption of the p53/p14(arf) pathway (defined as TP53 mutation or decreased p14(arf) expression, or both) was observed in 18 of 31 EGFR-mutated (58.1%) tumors and in 9 of 13 KRAS-mutated (69.2%) tumors.<bold>Conclusion: </bold>Inactivation of the p53/p14(arf) pathway is common but not systematic in EGFR- or KRAS-mutated lung adenocarcinomas. Our work highlights the need to better investigate the association between EGFR and KRAS mutations and alterations in tumor suppressor pathways.
- Publication
Clinical Lung Cancer, 2014, Vol 15, Issue 2, p124
- ISSN
1525-7304
- Publication type
journal article
- DOI
10.1016/j.cllc.2013.08.003