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Tracking the evolution of non-small-cell lung cancer (Record no. 76255)

MARC details
000 -LEADER
fixed length control field 02373cam a2200157 4500
001 - CONTROL NUMBER
control field NMDX7307
008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION
fixed length control field 120401t2017 xxu||||| |||| 00| 0 eng d
100 ## - MAIN ENTRY--PERSONAL NAME
Personal name Anand, G.
240 ## - UNIFORM TITLE
Uniform title <a href="New England Journal of Medicine">New England Journal of Medicine</a>
245 ## - TITLE STATEMENT
Title Tracking the evolution of non-small-cell lung cancer
260 ## - PUBLICATION, DISTRIBUTION, ETC. (IMPRINT)
Date of publication, distribution, etc. 2017
500 ## - GENERAL NOTE
General note NMUH Staff Publications
520 ## - SUMMARY, ETC.
Summary, etc. &lt;span style="font-size: 10pt;"&gt;Background Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC. Methods In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy. We sequenced and analyzed 327 tumor regions to define evolutionary histories, obtain a census of clonal and subclonal events, and assess the relationship between intratumor heterogeneity and recurrence-free survival. Results We observed widespread intratumor heterogeneity for both somatic copy-number alterations and mutations. Driver mutations in EGFR, MET, BRAF, and TP53 were almost always clonal. However, heterogeneous driver alterations that occurred later in evolution were found in more than 75% of the tumors and were common in PIK3CA and NF1 and in genes that are involved in chromatin modification and DNA damage response and repair. Genome doubling and ongoing dynamic chromosomal instability were associated with intratumor heterogeneity and resulted in parallel evolution of driver somatic copy-number alterations, including amplifications in CDK4, FOXA1, and BCL11A. Elevated copy-number heterogeneity was associated with an increased risk of recurrence or death (hazard ratio, 4.9; P=4.4×10-4), which remained significant in multivariate analysis. Conclusions Intratumor heterogeneity mediated through chromosome instability was associated with an increased risk of recurrence or death, a finding that supports the potential value of chromosome instability as a prognostic predictor.&lt;/span&gt;
856 ## - ELECTRONIC LOCATION AND ACCESS
Uniform Resource Identifier <a href="https://www.ncbi.nlm.nih.gov/pubmed/28445112">https://www.ncbi.nlm.nih.gov/pubmed/28445112</a>
856 ## - ELECTRONIC LOCATION AND ACCESS
Uniform Resource Identifier <a href="http://www.nejm.org/doi/pdf/10.1056/NEJMoa1616288">http://www.nejm.org/doi/pdf/10.1056/NEJMoa1616288</a>
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        Staff publications for NMDX Ferriman Information and Library Service (North Middlesex) Ferriman Information and Library Service (North Middlesex) Online 07/06/2022   07/06/2022 07/06/2022 UNKNOWN