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

9 Citations (Scopus)

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

Fingerprint

Colonic Neoplasms
Young Adult
Exome
Carrier Proteins
Breast Neoplasms
RNA Sequence Analysis
Frameshift Mutation
Mutation
Mutation Rate
Genes
Pediatrics
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Tricoli, J. V., Boardman, L. A., Patidar, R., Sindiri, S., Jang, J. S., Walsh, W. D., ... 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

A mutational comparison of adult and adolescent and young adult (AYA) colon cancer. / Tricoli, James V.; Boardman, Lisa Allyn; Patidar, Rajesh; Sindiri, Sivasish; Jang, Jin S.; Walsh, William D.; Mcgregor, Paul M.; Camalier, Corinne E.; Mehaffey, Michele G.; Furman, Wayne L.; Bahrami, Armita; Williams, P. Mickey; Lih, Chih Jian; Conley, Barbara A.; Khan, Javed.

In: Cancer, 01.01.2017.

Research output: Contribution to journalArticle

Tricoli, JV, Boardman, LA, Patidar, R, Sindiri, S, Jang, JS, Walsh, WD, Mcgregor, PM, Camalier, CE, Mehaffey, MG, Furman, WL, Bahrami, A, Williams, PM, Lih, CJ, Conley, BA & Khan, J 2017, 'A mutational comparison of adult and adolescent and young adult (AYA) colon cancer', Cancer. https://doi.org/10.1002/cncr.31136
Tricoli, James V. ; Boardman, Lisa Allyn ; Patidar, Rajesh ; Sindiri, Sivasish ; Jang, Jin S. ; Walsh, William D. ; Mcgregor, Paul M. ; Camalier, Corinne E. ; Mehaffey, Michele G. ; Furman, Wayne L. ; Bahrami, Armita ; Williams, P. Mickey ; Lih, Chih Jian ; Conley, Barbara A. ; Khan, Javed. / A mutational comparison of adult and adolescent and young adult (AYA) colon cancer. In: Cancer. 2017.
@article{4cde5d7a8c7d4b59a511b62a4859785a,
title = "A mutational comparison of adult and adolescent and young adult (AYA) colon 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.",
keywords = "Adolescent and young adult (AYA), Colon cancer, Exome sequencing, Mutation, RNA sequencing (RNASeq)",
author = "Tricoli, {James V.} and Boardman, {Lisa Allyn} and Rajesh Patidar and Sivasish Sindiri and Jang, {Jin S.} and Walsh, {William D.} and Mcgregor, {Paul M.} and Camalier, {Corinne E.} and Mehaffey, {Michele G.} and Furman, {Wayne L.} and Armita Bahrami and Williams, {P. Mickey} and Lih, {Chih Jian} and Conley, {Barbara A.} and Javed Khan",
year = "2017",
month = "1",
day = "1",
doi = "10.1002/cncr.31136",
language = "English (US)",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",

}

TY - JOUR

T1 - A mutational comparison of adult and adolescent and young adult (AYA) colon cancer

AU - Tricoli, James V.

AU - Boardman, Lisa Allyn

AU - Patidar, Rajesh

AU - Sindiri, Sivasish

AU - Jang, Jin S.

AU - Walsh, William D.

AU - Mcgregor, Paul M.

AU - Camalier, Corinne E.

AU - Mehaffey, Michele G.

AU - Furman, Wayne L.

AU - Bahrami, Armita

AU - Williams, P. Mickey

AU - Lih, Chih Jian

AU - Conley, Barbara A.

AU - Khan, Javed

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Adolescent and young adult (AYA)

KW - Colon cancer

KW - Exome sequencing

KW - Mutation

KW - RNA sequencing (RNASeq)

UR - http://www.scopus.com/inward/record.url?scp=85036525371&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85036525371&partnerID=8YFLogxK

U2 - 10.1002/cncr.31136

DO - 10.1002/cncr.31136

M3 - Article

C2 - 29194591

AN - SCOPUS:85036525371

JO - Cancer

JF - Cancer

SN - 0008-543X

ER -