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Comparative Study
. 2018 Mar 1;124(5):1070-1082.
doi: 10.1002/cncr.31136. Epub 2017 Nov 30.

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

James V Tricoli  1 , Lisa A Boardman  2 , Rajesh Patidar  3 , Sivasish Sindiri  3 , Jin S Jang  4 , William D Walsh  5 , Paul M McGregor 3rd  5 , Corinne E Camalier  5 , Michele G Mehaffey  5 , Wayne L Furman  6 , Armita Bahrami  7 , P Mickey Williams  5 , Chih-Jian Lih  5 , Barbara A Conley  1 , Javed Khan  3
Affiliations
Comparative Study

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

James V Tricoli et al. Cancer. .

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. Cancer 2018;124:1070-82. © 2017 American Cancer Society.

Keywords: RNA sequencing (RNASeq); adolescent and young adult (AYA); colon cancer; exome sequencing; mutation.

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Conflict of interest statement

Conflicts of Interest: None for any authors

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