Somatic substitution signature as an innovative tool in lung cancer diagnosis

Abstract Diagnosis of lung cancer can sometimes be challenging and is of major interest since effective molecular-guided therapies are available. Compounds of tobacco smoke may generate a specific substitutional signature in lung, which is the most exposed organ. To predict whether a tumor is of lun...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Stéphane Busca, Julia Salleron, Romain Boidot, Jean-Louis Merlin, Alexandre Harlé
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b87948ed20474dea8a6fabbf8e342a86
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b87948ed20474dea8a6fabbf8e342a86
record_format	dspace
spelling	oai:doaj.org-article:b87948ed20474dea8a6fabbf8e342a862021-12-02T15:10:03ZSomatic substitution signature as an innovative tool in lung cancer diagnosis10.1038/s41598-019-51155-32045-2322https://doaj.org/article/b87948ed20474dea8a6fabbf8e342a862019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-51155-3https://doaj.org/toc/2045-2322Abstract Diagnosis of lung cancer can sometimes be challenging and is of major interest since effective molecular-guided therapies are available. Compounds of tobacco smoke may generate a specific substitutional signature in lung, which is the most exposed organ. To predict whether a tumor is of lung origin or not, we developed and validated the EASILUNG (Exome And SIgnature LUNG) test based on the relative frequencies of somatic substitutions on coding non-transcribed DNA strands from whole-exome sequenced tumors. Data from 7,796 frozen tumor samples (prior to any treatment) from 32 TCGA solid cancer groups were used for its development. External validation was carried out on a local dataset of 196 consecutive routine exome results. Eight out of the 12 classes of substitutions were required to compute the EASILUNG signature that demonstrated good calibration and good discriminative power with a sensitivity of 83% and a specificity of 72% after recalibration on the external validation dataset. This innovative test may be helpful in medical decision-making in patients with unknown primary tumors potentially of lung origin and in the diagnosis of lung cancer in smokers.Stéphane BuscaJulia SalleronRomain BoidotJean-Louis MerlinAlexandre HarléNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-9 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stéphane Busca Julia Salleron Romain Boidot Jean-Louis Merlin Alexandre Harlé Somatic substitution signature as an innovative tool in lung cancer diagnosis
description	Abstract Diagnosis of lung cancer can sometimes be challenging and is of major interest since effective molecular-guided therapies are available. Compounds of tobacco smoke may generate a specific substitutional signature in lung, which is the most exposed organ. To predict whether a tumor is of lung origin or not, we developed and validated the EASILUNG (Exome And SIgnature LUNG) test based on the relative frequencies of somatic substitutions on coding non-transcribed DNA strands from whole-exome sequenced tumors. Data from 7,796 frozen tumor samples (prior to any treatment) from 32 TCGA solid cancer groups were used for its development. External validation was carried out on a local dataset of 196 consecutive routine exome results. Eight out of the 12 classes of substitutions were required to compute the EASILUNG signature that demonstrated good calibration and good discriminative power with a sensitivity of 83% and a specificity of 72% after recalibration on the external validation dataset. This innovative test may be helpful in medical decision-making in patients with unknown primary tumors potentially of lung origin and in the diagnosis of lung cancer in smokers.
format	article
author	Stéphane Busca Julia Salleron Romain Boidot Jean-Louis Merlin Alexandre Harlé
author_facet	Stéphane Busca Julia Salleron Romain Boidot Jean-Louis Merlin Alexandre Harlé
author_sort	Stéphane Busca
title	Somatic substitution signature as an innovative tool in lung cancer diagnosis
title_short	Somatic substitution signature as an innovative tool in lung cancer diagnosis
title_full	Somatic substitution signature as an innovative tool in lung cancer diagnosis
title_fullStr	Somatic substitution signature as an innovative tool in lung cancer diagnosis
title_full_unstemmed	Somatic substitution signature as an innovative tool in lung cancer diagnosis
title_sort	somatic substitution signature as an innovative tool in lung cancer diagnosis
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/b87948ed20474dea8a6fabbf8e342a86
work_keys_str_mv	AT stephanebusca somaticsubstitutionsignatureasaninnovativetoolinlungcancerdiagnosis AT juliasalleron somaticsubstitutionsignatureasaninnovativetoolinlungcancerdiagnosis AT romainboidot somaticsubstitutionsignatureasaninnovativetoolinlungcancerdiagnosis AT jeanlouismerlin somaticsubstitutionsignatureasaninnovativetoolinlungcancerdiagnosis AT alexandreharle somaticsubstitutionsignatureasaninnovativetoolinlungcancerdiagnosis
_version_	1718387775199248384

Somatic substitution signature as an innovative tool in lung cancer diagnosis

Ejemplares similares