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Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis.

Publication ,  Journal Article
Liu, W; Snell, JM; Jeck, WR; Hoadley, KA; Wilkerson, MD; Parker, JS; Patel, N; Mlombe, YB; Mulima, G; Liomba, NG; Wolf, LL; Shores, CG ...
Published in: JCI Insight
October 6, 2016

Esophageal squamous cell carcinoma (ESCC) is endemic in regions of sub-Saharan Africa (SSA), where it is the third most common cancer. Here, we describe whole-exome tumor/normal sequencing and RNA transcriptomic analysis of 59 patients with ESCC in Malawi. We observed similar genetic aberrations as reported in Asian and North American cohorts, including mutations of TP53, CDKN2A, NFE2L2, CHEK2, NOTCH1, FAT1, and FBXW7. Analyses for nonhuman sequences did not reveal evidence for infection with HPV or other occult pathogens. Mutational signature analysis revealed common signatures associated with aging, cytidine deaminase activity (APOBEC), and a third signature of unknown origin, but signatures of inhaled tobacco use, aflatoxin and mismatch repair were notably absent. Based on RNA expression analysis, ESCC could be divided into 3 distinct subtypes, which were distinguished by their expression of cell cycle and neural transcripts. This study demonstrates discrete subtypes of ESCC in SSA, and suggests that the endemic nature of this disease reflects exposure to a carcinogen other than tobacco and oncogenic viruses.

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Published In

JCI Insight

DOI

ISSN

2379-3708

Publication Date

October 6, 2016

Volume

1

Issue

16

Start / End Page

e88755

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tumor Suppressor Protein p53
  • Transcriptome
  • Transcription Factors
  • Mutation
  • Middle Aged
  • Male
  • Malawi
  • Humans
  • Gene Dosage
 

Citation

APA
Chicago
ICMJE
MLA
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Liu, W., Snell, J. M., Jeck, W. R., Hoadley, K. A., Wilkerson, M. D., Parker, J. S., … Sharpless, N. E. (2016). Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis. JCI Insight, 1(16), e88755. https://doi.org/10.1172/jci.insight.88755
Liu, Wenjin, Jeff M. Snell, William R. Jeck, Katherine A. Hoadley, Matthew D. Wilkerson, Joel S. Parker, Nirali Patel, et al. “Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis.JCI Insight 1, no. 16 (October 6, 2016): e88755. https://doi.org/10.1172/jci.insight.88755.
Liu W, Snell JM, Jeck WR, Hoadley KA, Wilkerson MD, Parker JS, et al. Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis. JCI Insight. 2016 Oct 6;1(16):e88755.
Liu, Wenjin, et al. “Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis.JCI Insight, vol. 1, no. 16, Oct. 2016, p. e88755. Pubmed, doi:10.1172/jci.insight.88755.
Liu W, Snell JM, Jeck WR, Hoadley KA, Wilkerson MD, Parker JS, Patel N, Mlombe YB, Mulima G, Liomba NG, Wolf LL, Shores CG, Gopal S, Sharpless NE. Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis. JCI Insight. 2016 Oct 6;1(16):e88755.

Published In

JCI Insight

DOI

ISSN

2379-3708

Publication Date

October 6, 2016

Volume

1

Issue

16

Start / End Page

e88755

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tumor Suppressor Protein p53
  • Transcriptome
  • Transcription Factors
  • Mutation
  • Middle Aged
  • Male
  • Malawi
  • Humans
  • Gene Dosage