Abstract
A new somatic mutation in the coding region of Kirsten rat sarcoma viral oncogene homolog gene (KRAS), G48A, has been identified in a patient with non-small cell lung cancer (NSCLC). No other mutations were found by screening several genes known to be mutated in NSCLC. The patient responded to first-line therapy and is still under maintenance treatment 18 months after diagnosis. Normal and cancer cells were engineered to express the KRAS(G48A) mutation. KRAS(G48A) overexpression did not change the growth or the response to treatment compared with KRAS(wild type)-expressing cells. Analysis of the structure of the KRAS(G48A) mutant predicted altered interactions with other proteins. Analysis of KRAS binding to B-Raf proto-oncogene, serine/threonine kinase showed that the KRAS(G48A) mutant behaves more like a wild-type than a classical KRAS(G12) mutant. In conclusion, this new mutation in the coding region of KRAS, found in NSCLC, does not induce phenotypic changes similar to those induced by G12 mutants but presumably affects KRAS binding to proteins other than B-Raf proto-oncogene, serine/threonine kinase.
| Original language | English |
|---|---|
| Pages (from-to) | 1170-1175 |
| Number of pages | 6 |
| Journal | Journal of Thoracic Oncology |
| Volume | 11 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2016 |
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Keywords
- Adenocarcinoma
- Gene mutation
- KRAS
- Non-small cell lung cancer
ASJC Scopus subject areas
- Oncology
- Pulmonary and Respiratory Medicine
Cite this
G48A, a new KRAS mutation found in lung adenocarcinoma. / Marabese, Mirko; Caiola, Elisa; Garassino, Marina C.; Rastelli, Giulio; Settanni, Giulio; Brugnara, Sonia; Broggini, Massimo; Ganzinelli, Monica.
In: Journal of Thoracic Oncology, Vol. 11, No. 7, 2016, p. 1170-1175.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - G48A, a new KRAS mutation found in lung adenocarcinoma
AU - Marabese, Mirko
AU - Caiola, Elisa
AU - Garassino, Marina C.
AU - Rastelli, Giulio
AU - Settanni, Giulio
AU - Brugnara, Sonia
AU - Broggini, Massimo
AU - Ganzinelli, Monica
PY - 2016
Y1 - 2016
N2 - A new somatic mutation in the coding region of Kirsten rat sarcoma viral oncogene homolog gene (KRAS), G48A, has been identified in a patient with non-small cell lung cancer (NSCLC). No other mutations were found by screening several genes known to be mutated in NSCLC. The patient responded to first-line therapy and is still under maintenance treatment 18 months after diagnosis. Normal and cancer cells were engineered to express the KRAS(G48A) mutation. KRAS(G48A) overexpression did not change the growth or the response to treatment compared with KRAS(wild type)-expressing cells. Analysis of the structure of the KRAS(G48A) mutant predicted altered interactions with other proteins. Analysis of KRAS binding to B-Raf proto-oncogene, serine/threonine kinase showed that the KRAS(G48A) mutant behaves more like a wild-type than a classical KRAS(G12) mutant. In conclusion, this new mutation in the coding region of KRAS, found in NSCLC, does not induce phenotypic changes similar to those induced by G12 mutants but presumably affects KRAS binding to proteins other than B-Raf proto-oncogene, serine/threonine kinase.
AB - A new somatic mutation in the coding region of Kirsten rat sarcoma viral oncogene homolog gene (KRAS), G48A, has been identified in a patient with non-small cell lung cancer (NSCLC). No other mutations were found by screening several genes known to be mutated in NSCLC. The patient responded to first-line therapy and is still under maintenance treatment 18 months after diagnosis. Normal and cancer cells were engineered to express the KRAS(G48A) mutation. KRAS(G48A) overexpression did not change the growth or the response to treatment compared with KRAS(wild type)-expressing cells. Analysis of the structure of the KRAS(G48A) mutant predicted altered interactions with other proteins. Analysis of KRAS binding to B-Raf proto-oncogene, serine/threonine kinase showed that the KRAS(G48A) mutant behaves more like a wild-type than a classical KRAS(G12) mutant. In conclusion, this new mutation in the coding region of KRAS, found in NSCLC, does not induce phenotypic changes similar to those induced by G12 mutants but presumably affects KRAS binding to proteins other than B-Raf proto-oncogene, serine/threonine kinase.
KW - Adenocarcinoma
KW - Gene mutation
KW - KRAS
KW - Non-small cell lung cancer
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UR - http://www.scopus.com/inward/citedby.url?scp=84978272047&partnerID=8YFLogxK
U2 - 10.1016/j.jtho.2016.03.013
DO - 10.1016/j.jtho.2016.03.013
M3 - Article
AN - SCOPUS:84978272047
VL - 11
SP - 1170
EP - 1175
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
SN - 1556-0864
IS - 7
ER -