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Background: The issue of overdiagnosis in low-dose computed tomography (LDCT) screening trials could be addressed by the development of complementary biomarkers able to improve detection of aggressive disease. The mutation profile of LDCT screening-detected lung tumors is currently unknown.

Methods: Targeted next-generation sequencing was performed on 94 LDCT screening-detected lung tumors. Associations with clinicopathologic features, survival, and the risk profile of a plasma microRNA signature classifier were analyzed.

Results: The mutational spectrum and frequency observed in screening series was similar to that reported in public data sets, although a larger number of tumors without mutations in driver genes was detected. The 5-year overall survival (OS) rates of patients with and without mutations in the tumors were 66% and 100%, respectively (p = 0.015). By combining the mutational status with the microRNA signature classifier risk profile, patients were stratified into three groups with 5-year OS rates ranging from 42% to 97% (p < 0.0001) and the prognostic value was significant after controlling for stage (p = 0.02).

Conclusion: Tumor mutational status along with a microRNA-based liquid biopsy can provide additional information in planning clinical follow-up in lung cancer LDCT screening programs.

Titel:	Mutational Profile from Targeted NGS Predicts Survival in LDCT Screening-Detected Lung Cancers.
Autor/in / Beteiligte Person:	Verri, C ; Borzi, C ; Holscher, T ; Dugo, M ; Devecchi, A ; Drake, K ; Sestini, S ; Suatoni, P ; Romeo, E ; Sozzi, G ; Pastorino, U ; Boeri, M
Link:	Full Text Finder (Volltext)
Zeitschrift:	Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, Jg. 12 (2017-06-01), Heft 6, S. 922-931
Veröffentlichung:	2016- : New York, NY : Elsevier ; <i>Original Publication</i>: Hagerstown, MD : Lippincott Williams & Wilkins, c2006-, 2017
Medientyp:	academicJournal
ISSN:	1556-1380 (electronic)
DOI:	10.1016/j.jtho.2017.03.001
Schlagwort:	Adenocarcinoma genetics Adenocarcinoma pathology Adult Carcinoma, Squamous Cell genetics Carcinoma, Squamous Cell pathology Early Detection of Cancer Female Follow-Up Studies Humans Lung Neoplasms genetics Lung Neoplasms pathology Male Middle Aged Prognosis Small Cell Lung Carcinoma genetics Small Cell Lung Carcinoma pathology Survival Rate Tomography, X-Ray Computed methods Adenocarcinoma mortality Biomarkers, Tumor genetics Carcinoma, Squamous Cell mortality High-Throughput Nucleotide Sequencing methods Lung Neoplasms mortality Mutation Small Cell Lung Carcinoma mortality
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [J Thorac Oncol] 2017 Jun; Vol. 12 (6), pp. 922-931. <i>Date of Electronic Publication: </i>2017 Mar 14. MeSH Terms: Mutation* ; Adenocarcinoma / mortality ; Biomarkers, Tumor / genetics ; Carcinoma, Squamous Cell / mortality ; High-Throughput Nucleotide Sequencing / methods ; Lung Neoplasms / mortality ; Small Cell Lung Carcinoma / mortality ; Adenocarcinoma / genetics ; Adenocarcinoma / pathology ; Adult ; Carcinoma, Squamous Cell / genetics ; Carcinoma, Squamous Cell / pathology ; Early Detection of Cancer ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms / genetics ; Lung Neoplasms / pathology ; Male ; Middle Aged ; Prognosis ; Small Cell Lung Carcinoma / genetics ; Small Cell Lung Carcinoma / pathology ; Survival Rate ; Tomography, X-Ray Computed / methods References: J Surg Oncol. 2013 Oct;108(5):280-6. (PMID: 23893464) ; N Engl J Med. 2011 Aug 4;365(5):395-409. (PMID: 21714641) ; JAMA. 2012 Jun 13;307(22):2418-29. (PMID: 22610500) ; J Surg Oncol. 2013 Oct;108(5):275-9. (PMID: 23918530) ; Clin Cancer Res. 2015 Jan 15;21(2):484-9. (PMID: 25593345) ; Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4525-9. (PMID: 24616506) ; Nat Cell Biol. 2014 Aug;16(8):717-27. (PMID: 25082194) ; J Thorac Oncol. 2016 Nov;11(11):1976-1983. (PMID: 27374456) ; Cancer J. 2012 May-Jun;18(3):268-74. (PMID: 22647364) ; Thorax. 2012 Apr;67(4):296-301. (PMID: 22286927) ; J Thorac Oncol. 2011 Nov;6(11):1841-8. (PMID: 21892105) ; Oncotarget. 2015 Oct 20;6(32):32868-77. (PMID: 26451608) ; J Thorac Oncol. 2016 May;11(5):693-699. (PMID: 26921675) ; Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13306-11. (PMID: 15329413) ; Transl Lung Cancer Res. 2015 Aug;4(4):327-38. (PMID: 26380174) ; Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):E2110-6. (PMID: 22753494) ; Cancer. 2014 Dec 1;120 Suppl 23:3781-92. (PMID: 25412390) ; Am J Respir Crit Care Med. 2016 Mar 1;193(5):534-41. (PMID: 26502000) ; Cancer Genet. 2015 Apr;208(4):152-5. (PMID: 25850996) ; N Engl J Med. 2006 Oct 26;355(17):1763-71. (PMID: 17065637) ; Biol Cell. 2015 Mar;107(3):61-77. (PMID: 25564937) ; Biomed Res Int. 2014;2014:364316. (PMID: 25386559) ; J Clin Oncol. 2014 Mar 10;32(8):768-73. (PMID: 24419137) ; Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3713-8. (PMID: 21300873) ; Am J Respir Crit Care Med. 2015 May 15;191(10):1166-75. (PMID: 25760561) ; Biometrics. 1982 Dec;38(4):921-32. (PMID: 7168795) ; Expert Rev Mol Diagn. 2015 Jun;15(6):801-13. (PMID: 25924864) ; PLoS One. 2016 Feb 26;11(2):e0149405. (PMID: 26919633) ; JAMA Intern Med. 2014 Feb 1;174(2):269-74. (PMID: 24322569) ; Chest. 2013 May;143(5 Suppl):e278S-e313S. (PMID: 23649443) ; Sci Transl Med. 2013 Oct 30;5(209):209ra153. (PMID: 24174329) ; Cell. 2012 Sep 14;150(6):1107-20. (PMID: 22980975) ; Br J Cancer. 2014 Sep 9;111(6):1222-9. (PMID: 25051406) ; N Engl J Med. 2008 Sep 25;359(13):1367-80. (PMID: 18815398) ; Molecules. 2014 Mar 10;19(3):3038-54. (PMID: 24619302) ; Lancet. 2003 Aug 23;362(9384):593-7. (PMID: 12944057) ; Oncotarget. 2016 Feb 16;7(7):8373-88. (PMID: 26840022) ; CA Cancer J Clin. 2013 Jan;63(1):11-30. (PMID: 23335087) ; J Natl Cancer Inst. 2015 Mar 19;107(6):djv063. (PMID: 25794889) ; Eur J Cancer Prev. 2012 May;21(3):308-15. (PMID: 22465911) Grant Information: U01 CA166905 United States CA NCI NIH HHS Contributed Indexing: Keywords: Low-dose computed tomography; Lung cancer; MicroRNA-based liquid biopsy; Mutational load; Next-generation sequencing Substance Nomenclature: 0 (Biomarkers, Tumor) Entry Date(s): Date Created: 20170318 Date Completed: 20180314 Latest Revision: 20191108 Update Code: 20231215 PubMed Central ID: PMC6832691

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Mutational Profile from Targeted NGS Predicts Survival in LDCT Screening-Detected Lung Cancers.