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Cancer. 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.

Author information

1
Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland.
2
Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
3
Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
4
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
5
Molecular Characterization and Assay Development Laboratory, Leidos, Frederick, Maryland.
6
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
7
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.

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

PMID:
29194591
PMCID:
PMC5821537
[Available on 2019-03-01]
DOI:
10.1002/cncr.31136

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