Detection of somatic TP53 mutation in surgically resected small-cell lung cancer by targeted exome sequencing: association with longer relapse-free survival

Heliyon
Hiroshi YokouchiHiroshi Isobe

Abstract

Few reports have explored clinical biomarkers, including those identified by targeted exome sequencing (TES) of surgically resected small-cell lung cancer (SCLC) and correlation with patient survival. We collected formalin-fixed paraffin-embedded tumor samples from 127 patients with SCLC who had undergone surgery and analysed nonsynonymous somatic gene mutation profiles by TES of 26 cancer-related genes using next-generation sequencing (NGS) and web databases (UMIN Registration No. 000010117). We detected 38 nonsynonymous somatic tumor protein p53 (TP53) mutations in 43 (54.4%) patients. Among these TP53 lesions, we identified clinically relevant mutations including those encoding Y220C, R248W, R249M, M237I, and R273L substitutions in the p53 protein. These mutations have been reported to be associated with certain clinical outcomes or biology in other types of malignancies but not in SCLC. Moreover, nonsynonymous somatic mutations of TP53 were positively associated with relapse-free survival (RFS) (median, 17.33 months [95% confidence interval (CI), 3.86-30.79] in a mutation-positive group vs 10.39 months (6.96-13.82) in a mutation-negative group, p = 0.042). Multivariate analysis revealed that nonsynonymous somatic TP53 mutat...Continue Reading

Associated Datasets

Oct 16, 2019·Hiroshi Yokouchi

References

Sep 1, 2007·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Peter GoldstrawUNKNOWN Participating Institutions
Nov 2, 2007·Nature Reviews. Cancer·Robin MathewEileen White
Dec 21, 2007·The New England Journal of Medicine·M Luana PoetaWayne M Koch
Mar 22, 2008·Cell Death and Differentiation·R U JänickeK Schulze-Osthoff
Mar 13, 2009·Genes & Development·Andrew R J YoungMasashi Narita
Dec 18, 2009·Nature·Erin D PleasancePeter J Campbell
Oct 6, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Marc PeetersJennifer Gansert
May 14, 2011·Lancet·Jan P van MeerbeeckDirk K M De Ruysscher
Jun 28, 2011·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Remi-Martin LabergePierre-Yves Desprez
Jan 12, 2013·Journal of the National Comprehensive Cancer Network : JNCCN·Gregory P KalemkerianUNKNOWN National Comprehensive Cancer Network
Apr 9, 2013·Cell·Amaia LujambioScott W Lowe
Jan 7, 2014·Nature·Akinyemi I OjesinaMatthew Meyerson
May 23, 2014·JAMA : the Journal of the American Medical Association·Mark G KrisPaul A Bunn
Aug 15, 2014·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Shigeki UmemuraKoichi Goto
Sep 16, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elizabeth K ZiemkeJudith S Sebolt-Leopold
Dec 17, 2015·Scientific Reports·Ching-Hung LinAnn-Lii Cheng
Dec 23, 2016·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Arnaud AugertDavid MacPherson
May 11, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·David M HymanBarry S Taylor
Aug 10, 2017·Frontiers in Immunology·Michael SelemanJanet Chou
Sep 9, 2017·Cell·Edward R Kastenhuber, Scott W Lowe
Aug 31, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A KronJ Wolf
Oct 13, 2018·Haematologica·Katharina T ProchazkaHeinz Sill
Dec 12, 2018·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Hibiki UdagawaKoichi Goto
Feb 19, 2019·Cytokine·Stéphane Lopes-PacienciaGerardo Ferbeyre
May 28, 2019·Advances in Experimental Medicine and Biology·D Prabavathy, Niveditha Ramadoss
Nov 1, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C LeducUNKNOWN French Cooperative Thoracic Intergroup (IFCT)
Mar 8, 2020·Journal of Cell Science·Julianna BlagihKaren H Vousden

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Methods Mentioned

BETA
exome sequencing
surgical resection
Assay
biopsy

Software Mentioned

SnpEff
GATK UnifiedGenotyper
IndelRealigner
SPSS
RealignerTargetCreator
IntOGen
Miseq Reporter
GATK VariantFiltration
BioReT System
Genome Analysis Toolkit ( GATK )

Related Concepts

Related Feeds

Cancer Sequencing

Several sequencing approaches are employed to understand and examine tumor development and progression. These include whole genome as well as RNA sequencing. Here is the latest research on cancer sequencing.