McGregor, Paul M.

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 .