G48A, a new KRAS mutation found in lung adenocarcinoma

Mirko Marabese, Elisa Caiola, Marina C. Garassino, Giulio Rastelli, Giulio Settanni, Sonia Brugnara, Massimo Broggini, Monica Ganzinelli

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)1170-1175
Number of pages6
JournalJournal of Thoracic Oncology
Volume11
Issue number7
DOIs
Publication statusPublished - 2016

Fingerprint

Non-Small Cell Lung Carcinoma
Mutation
Proto-Oncogenes
Protein-Serine-Threonine Kinases
Oncogenes
Sarcoma
Genes
Carrier Proteins
Therapeutics
Adenocarcinoma of lung
Growth
Neoplasms
Proteins
IgA receptor

Keywords

  • Adenocarcinoma
  • Gene mutation
  • KRAS
  • Non-small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Marabese, M., Caiola, E., Garassino, M. C., Rastelli, G., Settanni, G., Brugnara, S., ... Ganzinelli, M. (2016). G48A, a new KRAS mutation found in lung adenocarcinoma. Journal of Thoracic Oncology, 11(7), 1170-1175. https://doi.org/10.1016/j.jtho.2016.03.013

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 journalArticle

Marabese, M, Caiola, E, Garassino, MC, Rastelli, G, Settanni, G, Brugnara, S, Broggini, M & Ganzinelli, M 2016, 'G48A, a new KRAS mutation found in lung adenocarcinoma', Journal of Thoracic Oncology, vol. 11, no. 7, pp. 1170-1175. https://doi.org/10.1016/j.jtho.2016.03.013
Marabese, Mirko ; Caiola, Elisa ; Garassino, Marina C. ; Rastelli, Giulio ; Settanni, Giulio ; Brugnara, Sonia ; Broggini, Massimo ; Ganzinelli, Monica. / G48A, a new KRAS mutation found in lung adenocarcinoma. In: Journal of Thoracic Oncology. 2016 ; Vol. 11, No. 7. pp. 1170-1175.
@article{68ddf4200a6b42a991e7156d4693b2c8,
title = "G48A, a new KRAS mutation found in lung adenocarcinoma",
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.",
keywords = "Adenocarcinoma, Gene mutation, KRAS, Non-small cell lung cancer",
author = "Mirko Marabese and Elisa Caiola and Garassino, {Marina C.} and Giulio Rastelli and Giulio Settanni and Sonia Brugnara and Massimo Broggini and Monica Ganzinelli",
year = "2016",
doi = "10.1016/j.jtho.2016.03.013",
language = "English",
volume = "11",
pages = "1170--1175",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "Elsevier Inc.",
number = "7",

}

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

UR - http://www.scopus.com/inward/record.url?scp=84978272047&partnerID=8YFLogxK

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 -