Oncology Central

Studies reveal genomic diversity of individual lung tumors

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A study led by researchers from the University of Texas MD Anderson Cancer Center (TX, USA), and published recently in Science, has addressed genomic heterogeneity in lung tumors. The team conducted whole-exome sequencing on 48 tumor regions from 11 surgically removed localized lung adenocarcinomas. A total of 7269 mutations were identified and, on average, 76% were found across all regions of the same tumor.

At a median follow-up of 21 months, three of the 11 patients had experienced disease relapse. At relapse, all three had a larger proportions of branch mutations (40%) limited to a few or even one region of the tumor, compared with a proportion of only 17% in non-relapsed patients.

At present, the small sample number limits the ability to draw conclusions from this work; larger studies will be required to confirm the relationship between relapse and the burden of branch mutations. The team is currently launching a larger study focusing on early-stage lung adenocarcinomas to study the associations between branch mutations and postsurgical relapse. It is hoped that the findings of this study might lead to stratification of patients at higher risk of relapse and allow for clinical trials of postsurgical drug treatment to prevent its occurrence.

“This indicates that a single biopsy, sequenced at appropriate depth, may prove to be very informative regarding mutations in known cancer genes in this group of lung cancers,” explained senior author Andrew Futreal, (MD Anderson). “If the correlation holds, that implies that some aspect of these branch mutations may be driving relapse, either by being a surrogate of some biological aspect of the tumor that we do not yet recognize or there being mutations occurring later that impart more aggressive characteristics, or some combination of the two.”

A companion study documenting the same conclusions has been conducted by researchers from Cancer Research UK and will be published in Science.

Sources: Zhang J, Fujimoto J, Zhang J et al. Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science. 346 (6206):256 (2014); MD Anderson Cancer Center news release

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