An integrated inspection of the somatic mutations in a lung squamous cell carcinoma using next-generation sequencing.

Squamous cell carcinoma (SCC) of the lung kills over 350,000 people annually worldwide, and is the main lung cancer histotype with no targeted treatments. High-coverage whole-genome sequencing of the other main subtypes, small-cell and adenocarcinoma, gave insights into carcinogenic mechanisms and d...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Lucy F Stead, Philip Egan, Aoife Devery, Caroline Conway, Catherine Daly, Stefano Berri, Henry Wood, Ornella Belvedere, Kostas Papagiannopoulos, Anderson Ryan, Pamela Rabbitts
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2013
Materias:
R
Q
Acceso en línea:https://doaj.org/article/0a9e99c83e624e189049beb7f1b2a024
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:0a9e99c83e624e189049beb7f1b2a024
record_format dspace
spelling oai:doaj.org-article:0a9e99c83e624e189049beb7f1b2a0242021-11-18T08:47:31ZAn integrated inspection of the somatic mutations in a lung squamous cell carcinoma using next-generation sequencing.1932-620310.1371/journal.pone.0078823https://doaj.org/article/0a9e99c83e624e189049beb7f1b2a0242013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24244370/?tool=EBIhttps://doaj.org/toc/1932-6203Squamous cell carcinoma (SCC) of the lung kills over 350,000 people annually worldwide, and is the main lung cancer histotype with no targeted treatments. High-coverage whole-genome sequencing of the other main subtypes, small-cell and adenocarcinoma, gave insights into carcinogenic mechanisms and disease etiology. The genomic complexity within the lung SCC subtype, as revealed by The Cancer Genome Atlas, means this subtype is likely to benefit from a more integrated approach in which the transcriptional consequences of somatic mutations are simultaneously inspected. Here we present such an approach: the integrated analysis of deep sequencing data from both the whole genome and whole transcriptome (coding and non-coding) of LUDLU-1, a SCC lung cell line. Our results show that LUDLU-1 lacks the mutational signature that has been previously associated with tobacco exposure in other lung cancer subtypes, and suggests that DNA-repair efficiency is adversely affected; LUDLU-1 contains somatic mutations in TP53 and BRCA2, allelic imbalance in the expression of two cancer-associated BRCA1 germline polymorphisms and reduced transcription of a potentially endogenous PARP2 inhibitor. Functional assays were performed and compared with a control lung cancer cell line. LUDLU-1 did not exhibit radiosensitisation or an increase in sensitivity to PARP inhibitors. However, LUDLU-1 did exhibit small but significant differences with respect to cisplatin sensitivity. Our research shows how integrated analyses of high-throughput data can generate hypotheses to be tested in the lab.Lucy F SteadPhilip EganAoife DeveryCaroline ConwayCatherine DalyStefano BerriHenry WoodOrnella BelvedereKostas PapagiannopoulosAnderson RyanPamela RabbittsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e78823 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Lucy F Stead
Philip Egan
Aoife Devery
Caroline Conway
Catherine Daly
Stefano Berri
Henry Wood
Ornella Belvedere
Kostas Papagiannopoulos
Anderson Ryan
Pamela Rabbitts
An integrated inspection of the somatic mutations in a lung squamous cell carcinoma using next-generation sequencing.
description Squamous cell carcinoma (SCC) of the lung kills over 350,000 people annually worldwide, and is the main lung cancer histotype with no targeted treatments. High-coverage whole-genome sequencing of the other main subtypes, small-cell and adenocarcinoma, gave insights into carcinogenic mechanisms and disease etiology. The genomic complexity within the lung SCC subtype, as revealed by The Cancer Genome Atlas, means this subtype is likely to benefit from a more integrated approach in which the transcriptional consequences of somatic mutations are simultaneously inspected. Here we present such an approach: the integrated analysis of deep sequencing data from both the whole genome and whole transcriptome (coding and non-coding) of LUDLU-1, a SCC lung cell line. Our results show that LUDLU-1 lacks the mutational signature that has been previously associated with tobacco exposure in other lung cancer subtypes, and suggests that DNA-repair efficiency is adversely affected; LUDLU-1 contains somatic mutations in TP53 and BRCA2, allelic imbalance in the expression of two cancer-associated BRCA1 germline polymorphisms and reduced transcription of a potentially endogenous PARP2 inhibitor. Functional assays were performed and compared with a control lung cancer cell line. LUDLU-1 did not exhibit radiosensitisation or an increase in sensitivity to PARP inhibitors. However, LUDLU-1 did exhibit small but significant differences with respect to cisplatin sensitivity. Our research shows how integrated analyses of high-throughput data can generate hypotheses to be tested in the lab.
format article
author Lucy F Stead
Philip Egan
Aoife Devery
Caroline Conway
Catherine Daly
Stefano Berri
Henry Wood
Ornella Belvedere
Kostas Papagiannopoulos
Anderson Ryan
Pamela Rabbitts
author_facet Lucy F Stead
Philip Egan
Aoife Devery
Caroline Conway
Catherine Daly
Stefano Berri
Henry Wood
Ornella Belvedere
Kostas Papagiannopoulos
Anderson Ryan
Pamela Rabbitts
author_sort Lucy F Stead
title An integrated inspection of the somatic mutations in a lung squamous cell carcinoma using next-generation sequencing.
title_short An integrated inspection of the somatic mutations in a lung squamous cell carcinoma using next-generation sequencing.
title_full An integrated inspection of the somatic mutations in a lung squamous cell carcinoma using next-generation sequencing.
title_fullStr An integrated inspection of the somatic mutations in a lung squamous cell carcinoma using next-generation sequencing.
title_full_unstemmed An integrated inspection of the somatic mutations in a lung squamous cell carcinoma using next-generation sequencing.
title_sort integrated inspection of the somatic mutations in a lung squamous cell carcinoma using next-generation sequencing.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/0a9e99c83e624e189049beb7f1b2a024
work_keys_str_mv AT lucyfstead anintegratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT philipegan anintegratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT aoifedevery anintegratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT carolineconway anintegratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT catherinedaly anintegratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT stefanoberri anintegratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT henrywood anintegratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT ornellabelvedere anintegratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT kostaspapagiannopoulos anintegratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT andersonryan anintegratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT pamelarabbitts anintegratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT lucyfstead integratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT philipegan integratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT aoifedevery integratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT carolineconway integratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT catherinedaly integratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT stefanoberri integratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT henrywood integratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT ornellabelvedere integratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT kostaspapagiannopoulos integratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT andersonryan integratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
AT pamelarabbitts integratedinspectionofthesomaticmutationsinalungsquamouscellcarcinomausingnextgenerationsequencing
_version_ 1718421305361956864