A mutational comparison of adult and adolescent and young adult (AYA) colon cancer

James V. Tricoli, Lisa Allyn Boardman, Rajesh Patidar, Sivasish Sindiri, Jin S. Jang, William D. Walsh, Paul M. Mcgregor, Corinne E. Camalier, Michele G. Mehaffey, Wayne L. Furman, Armita Bahrami, P. Mickey Williams, Chih Jian Lih, Barbara A. Conley, Javed Khan

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

BACKGROUND: It is possible that the relative lack of progress in treatment outcomes among adolescent and young adult (AYA) patients with cancer is caused by a difference in disease biology compared with the corresponding diseases in younger and older individuals. There is evidence that colon cancer is more aggressive and has a poorer prognosis in AYA patients than in older adult patients. METHODS: To further understand the molecular basis for this difference, whole-exome sequencing was conducted on a cohort of 30 adult, 30 AYA, and 2 pediatric colon cancers. RESULTS: A statistically significant difference in mutational frequency was observed between AYA and adult samples in 43 genes, including ROBO1, MYC binding protein 2 (MYCBP2), breast cancer 2 (early onset) (BRCA2), MAP3K3, MCPH1, RASGRP3, PTCH1, RAD9B, CTNND1, ATM, NF1; KIT, PTEN, and FBXW7. Many of these mutations were nonsynonymous, missense, stop-gain, or frameshift mutations that were damaging. Next, RNA sequencing was performed on a subset of the samples to confirm the mutations identified by exome sequencing. This confirmation study verified the presence of a significantly greater frequency of damaging mutations in AYA compared with adult colon cancers for 5 of the 43 genes (MYCBP2, BRCA2, PHLPP1, TOPORS, and ATR). CONCLUSIONS: The current results provide the rationale for a more comprehensive study with a larger sample set and experimental validation of the functional impact of the identified variants along with their contribution to the biologic and clinical characteristics of AYA colon cancer.

Original languageEnglish (US)
JournalCancer
DOIs
StateAccepted/In press - Jan 1 2017

Keywords

  • Adolescent and young adult (AYA)
  • Colon cancer
  • Exome sequencing
  • Mutation
  • RNA sequencing (RNASeq)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Tricoli, J. V., Boardman, L. A., Patidar, R., Sindiri, S., Jang, J. S., Walsh, W. D., Mcgregor, P. M., Camalier, C. E., Mehaffey, M. G., Furman, W. L., Bahrami, A., Williams, P. M., Lih, C. J., Conley, B. A., & Khan, J. (Accepted/In press). A mutational comparison of adult and adolescent and young adult (AYA) colon cancer. Cancer. https://doi.org/10.1002/cncr.31136