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Colon
Original article
The somatic mutation landscape of premalignant colorectal adenoma
  1. Shu-Hong Lin1,2,
  2. Gottumukkala S Raju3,
  3. Chad Huff1,
  4. Yuanqing Ye1,
  5. Jian Gu1,
  6. Jiun-Sheng Chen1,2,
  7. Michelle A T Hildebrandt1,
  8. Han Liang4,
  9. David G Menter5,
  10. Jeffery Morris6,
  11. Ernest Hawk7,
  12. John R Stroehlein3,
  13. Andrew Futreal8,
  14. Scott Kopetz5,
  15. Lopa Mishra3,
  16. Xifeng Wu1
  1. 1 Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  2. 2 The University of Texas Graduate School of Biomedical Sciences at Houston and MD Anderson Cancer Center, Houston, Texas, USA
  3. 3 Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  4. 4 Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  5. 5 Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  6. 6 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  7. 7 Division of Cancer Prevention and Population Science, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  8. 8 Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  1. Correspondence to Dr Xifeng Wu, Department of Epidemiology, Unit 1340, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA; xwu{at}mdanderson.org

Abstract

Objective There are few studies which characterised the molecular alterations in premalignant colorectal adenomas. Our major goal was to establish colorectal adenoma genome atlas and identify molecular markers of progression from colorectal adenoma to adenocarcinoma.

Design Whole-exome sequencing and targeted sequencing were carried out in 149 adenoma samples and paired blood from patients with conventional adenoma or sessile serrated adenoma to characterise the somatic mutation landscape for premalignant colorectal lesions. The identified somatic mutations were compared with those in colorectal cancer (CRC) samples from The Cancer Genome Atlas. A supervised random forest model was employed to identify gene panels differentiating adenoma from CRC.

Results Similar somatic mutation frequencies, but distinctive driver mutations, were observed in sessile serrated adenomas and conventional adenomas. The final model included 20 genes and was able to separate the somatic mutation profile of colorectal adenoma and adenocarcinoma with an area under the curve of 0.941.

Conclusion The findings of this project hold potential to better identify patients with adenoma who may be candidates for targeted surveillance programmes and preventive interventions to reduce the incidence of CRC.

  • colorectal adenoma
  • somatic mutation
  • sessile serrated adenoma
  • conventional adenoma

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/gutjnl-2016-313573

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    Footnotes

    • SK, LM and XW contributed equally.

    • S-HL, GSR and CH contributed equally.

    • Contributors Study design: GSR, XW, SK, LM, EH. Study recruitment, data and biospecimen collection and management: GSR, JRS, LM, XW. Bioinformatic analysis: SHL, CH, YY, JSC, HL, AF. Statistical analysis: SHL, YY. Biological annotation: SHL, JG, MATH, XW. Primary results interpretation: SHL, DGM, JM, AF, SK, XW. Manuscript drafting: SHL, YY, XW. All authors contributed to and critically reviewed the manuscript.

    • Funding This work was supported in part by the Colorectal Cancer Moon Shot Program, the Premalignant Genome Atlas Program, and the Center for Translational and Public Health Genomics, Duncan Family Institute for Cancer Prevention and Risk Assessment, The University of Texas MD Anderson Cancer Center.

    • Competing interests None declared.

    • Patient consent This manuscript only contains deidentified information which does not track back to patients. All patients have signed an MD Anderson consent form when they enrolled in our study.

    • Ethics approval Institutional Review Board of MD Anderson Cancer Center.

    • Provenance and peer review Not commissioned; externally peer reviewed.