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17-12-2014 | Article

Single biopsy site may reveal all lung adenocarcinoma genetic mutations


Free abstract

medwireNews: Genetic sequencing of a single tumour site sample may be adequate for identifying cancer gene mutations in patients with lung andenocarcinoma, research published in Science suggests.

This findings is in contrast to those of earlier renal cell carcinoma studies which demonstrated significant intratumour heterogeneity (ITH), indicating that a single biopsy was not sufficient to detect all relevant mutations in this tumour type, report Andrew Futreal (University of Texas MD Anderson Cancer Center, Houston, USA) and co-authors.

To determine the degree of ITH in lung cancer, the team performed multiregion whole-exome sequencing on 48 tumour regions samples from 11 patients with stage I, II or III localised lung adenocarcinomas.

There was significant heterogeneity in the number of mutations detected per tumour, independent of patient age, gender, smoking status and tumour characteristics, but 76% of mutations were detected in all regions of each tumour.

The team used a “tree” structure to characterise mutations as having appeared in all tumour regions sampled (the trunk), in some regions (the branches) or in only one region (a private branch).

Thirteen of 14 known cancer mutations were found in the phylogenetic trunks, as well all amplifications and deletions of known cancer genes, suggesting that “these mutations were acquired relatively early during evolution of these 11 tumors”, and may “drive tumor development”, write Futreal et al.

Over 21 months of follow-up, three patients experienced disease relapse and analysis revealed that their tumours had a higher proportion of mutations in the branches and private branches of their phylogenetic trees than those without relapse (mean; 40 vs 17%).

“Although the sample size is small, these findings suggest the possibility that subclonal mutations may be important for cancer progression and that larger subclonal mutation fraction may be associated with an increased likelihood of postsurgical relapse in this subset of lung adenocarcinoma patients”, the researchers hypothesise.

Further analysis revealed that mutation profiles varied significantly between patients who smoked and those who did not and that 28% of mutations had the base substitution pattern expected if the process had been mediated by APOBEC mRNA editing enzymes.

The authors observe that as patients with localised non-small-cell lung cancer patients undergo resection routinely, “there is an opportunity to confirm these preliminary observations by deep sequencing multiregion samples obtained from resected tumors.”

They therefore conclude: “The questions of whether sequencing targeted cancer gene panels versus [whole-exome sequencing] will yield sufficient mutation data for meaningful analyses and the most appropriate algorithms for analyses will need to be addressed in order to fully test if the clinical correlation suggested in these data are borne out in larger patient cohorts.”

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2014

By Lynda Williams, Senior medwireNews Reporter