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Comparative Study
. 2014 Jul 15;20(14):3842-8.
doi: 10.1158/1078-0432.CCR-14-0565. Epub 2014 May 29.

Squamous cell carcinoma of the oral tongue in young non-smokers is genomically similar to tumors in older smokers

Curtis R Pickering  1 , Jiexin Zhang  2 , David M Neskey  1 , Mei Zhao  1 , Samar A Jasser  1 , Jiping Wang  1 , Alexandra Ward  1 , C Jillian Tsai  3 , Marcus V Ortega Alves  1 , Jane H Zhou  4 , Jennifer Drummond  5 , Adel K El-Naggar  4 , Richard Gibbs  6 , John N Weinstein  7 , David A Wheeler  5 , Jing Wang  2 , Mitchell J Frederick  1 , Jeffrey N Myers  8
Affiliations
Comparative Study

Squamous cell carcinoma of the oral tongue in young non-smokers is genomically similar to tumors in older smokers

Curtis R Pickering et al. Clin Cancer Res. .

Abstract

Purpose: Epidemiologic studies have identified an increasing incidence of squamous cell carcinoma of the oral tongue (SCCOT) in younger patients.

Experimental design: DNA isolated from tongue tumors of young (<45 years, non-smokers) and old (>45 years) patients at was subjected to whole-exome sequencing and copy-number analysis. These data were compared with data from similar patients in the TCGA (The Cancer Genome Atlas) project.

Results: In this study, we found that gene-specific mutation and copy-number alteration frequencies were similar between young and old patients with SCCOT in two independent cohorts. Likewise, the types of base changes observed in the young cohort were similar to those in the old cohort even though they differed in smoking history. TCGA data also demonstrate that the genomic effects of smoking are tumor site-specific, and we find that smoking has only a minor impact on the types of mutations observed in SCCOT.

Conclusions: Overall, tumors from young patients with SCCOT appear genomically similar to those of older patients with SCCOT, and the cause for the increasing incidence of young SCCOT remains unknown. These data indicate that the functional impact of smoking on carcinogenesis in SCCOT is still poorly understood.

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Figures

Figure 1
Figure 1
Frequency of common genomic alterations in YT and OT. The frequency of each event in the MDA cohort is shown by a bar to the left of center and the frequency in the TCGA cohort is shown by a bar to the right of center.
Figure 2
Figure 2
Analysis of mutation profiles. A) The frequency of each type of single base substitution is indicated by a different color in each annotated HNSC cohort. B) Frequency distributions by smoking status and tissue site. C) Differences in frequency between 2 cohorts. The sample name indicates which samples were compared. For example S-NS indicates that the frequency in the NS cohort was subtracted from the frequency in the S cohort, therefore a positive result is a higher frequency in the S cohort. * p<0.0001, # p<0.001, ^ p<0.01. Abbreviations: MDA – MD Anderson cohort, TCGA – The Cancer Genome Atlas cohort, YT – young tongue SCC, OT – old tongue SCC, HNSC – TCGA HNSCC cohort, HPV+ – human papilloma virus positive tumors from TCGA cohort, LUAD – TCGA lung adenocarcinoma, BLCA – TCGA bladder urothelial carcinoma, S – smokers, NS – non-smokers, YT/OT – combined TCGA young tongue and old tongue cohorts.
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