Identification of a Novel Fusion Gene, FAM174A-WWC1, in Early-Onset Colorectal Cancer

Establishment and Characterization of Four Human Cancer Cell Lines from Early-Onset Colorectal Cancers

Soon Chan Kim, Ru Mi Shin, Ha Young Seo, Minjung Kim, Ji Won Park, Seung-Yong Jeong, Ja-Lok Ku

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and represents the second most common cause of all cancer-related deaths in Korea. Although epidemiological data indicate a sharp increase in the incidence of CRC among individuals older than 50 years, more than 10% of CRCs occur before reaching 50. These are known as early-onset CRCs (EOCRCs) and are likely to be suggestive of hereditary predisposition. However, known familial CRC syndromes account for only 20% of genetic aberrations of EOCRC, and the remaining 80% are still in question. Therefore, we aimed to establish reproducible biological resources and contribute to expand the mutation database of EOCRC. Four cell lines derived from the original tumor mass of CRC patients diagnosed under age 30 years were established, and next-generation sequencing technique was used to identify the genetic features of EOCRC. We have identified one novel fusion gene, FAM174A-WWC1, and analyzed its functional role. The induction of FAM174A-WWC1 to normal fibroblast caused alternations in cellular morphology as well as intercellular expression of E-cadherin and N-cadherin. Moreover, WWC1 carrying the fused FAM174A domain not only abrogated the membrane expression of YAP1 but also significantly increased the levels of nucleic YAP1. As a result, the FAM174A-WWC1 expression increased the oncogenic capacity and invasiveness of normal fibroblasts, which suggests its role as a potential driver mutation of EOCRC.

Original languageEnglish
Pages (from-to)1185-1195
Number of pages11
JournalTranslational Oncology
Volume12
Issue number9
Early online date19 Jun 2019
DOIs
StatePublished - 1 Sep 2019

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Gene Fusion
Colorectal Neoplasms
Cell Line
Cadherins
Neoplasms
Fibroblasts
Mutation
Korea
Databases
Membranes
Incidence

Cite this

@article{282b69ca38e94d1a8bd033a868e363af,
title = "Identification of a Novel Fusion Gene, FAM174A-WWC1, in Early-Onset Colorectal Cancer: Establishment and Characterization of Four Human Cancer Cell Lines from Early-Onset Colorectal Cancers",
abstract = "Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and represents the second most common cause of all cancer-related deaths in Korea. Although epidemiological data indicate a sharp increase in the incidence of CRC among individuals older than 50 years, more than 10{\%} of CRCs occur before reaching 50. These are known as early-onset CRCs (EOCRCs) and are likely to be suggestive of hereditary predisposition. However, known familial CRC syndromes account for only 20{\%} of genetic aberrations of EOCRC, and the remaining 80{\%} are still in question. Therefore, we aimed to establish reproducible biological resources and contribute to expand the mutation database of EOCRC. Four cell lines derived from the original tumor mass of CRC patients diagnosed under age 30 years were established, and next-generation sequencing technique was used to identify the genetic features of EOCRC. We have identified one novel fusion gene, FAM174A-WWC1, and analyzed its functional role. The induction of FAM174A-WWC1 to normal fibroblast caused alternations in cellular morphology as well as intercellular expression of E-cadherin and N-cadherin. Moreover, WWC1 carrying the fused FAM174A domain not only abrogated the membrane expression of YAP1 but also significantly increased the levels of nucleic YAP1. As a result, the FAM174A-WWC1 expression increased the oncogenic capacity and invasiveness of normal fibroblasts, which suggests its role as a potential driver mutation of EOCRC.",
author = "Kim, {Soon Chan} and Shin, {Ru Mi} and Seo, {Ha Young} and Minjung Kim and Park, {Ji Won} and Seung-Yong Jeong and Ja-Lok Ku",
note = "Copyright {\circledC} 2019 The Authors. Published by Elsevier Inc. All rights reserved.",
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Identification of a Novel Fusion Gene, FAM174A-WWC1, in Early-Onset Colorectal Cancer : Establishment and Characterization of Four Human Cancer Cell Lines from Early-Onset Colorectal Cancers. / Kim, Soon Chan; Shin, Ru Mi; Seo, Ha Young; Kim, Minjung; Park, Ji Won; Jeong, Seung-Yong; Ku, Ja-Lok.

In: Translational Oncology, Vol. 12, No. 9, 01.09.2019, p. 1185-1195.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Identification of a Novel Fusion Gene, FAM174A-WWC1, in Early-Onset Colorectal Cancer

T2 - Establishment and Characterization of Four Human Cancer Cell Lines from Early-Onset Colorectal Cancers

AU - Kim, Soon Chan

AU - Shin, Ru Mi

AU - Seo, Ha Young

AU - Kim, Minjung

AU - Park, Ji Won

AU - Jeong, Seung-Yong

AU - Ku, Ja-Lok

N1 - Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and represents the second most common cause of all cancer-related deaths in Korea. Although epidemiological data indicate a sharp increase in the incidence of CRC among individuals older than 50 years, more than 10% of CRCs occur before reaching 50. These are known as early-onset CRCs (EOCRCs) and are likely to be suggestive of hereditary predisposition. However, known familial CRC syndromes account for only 20% of genetic aberrations of EOCRC, and the remaining 80% are still in question. Therefore, we aimed to establish reproducible biological resources and contribute to expand the mutation database of EOCRC. Four cell lines derived from the original tumor mass of CRC patients diagnosed under age 30 years were established, and next-generation sequencing technique was used to identify the genetic features of EOCRC. We have identified one novel fusion gene, FAM174A-WWC1, and analyzed its functional role. The induction of FAM174A-WWC1 to normal fibroblast caused alternations in cellular morphology as well as intercellular expression of E-cadherin and N-cadherin. Moreover, WWC1 carrying the fused FAM174A domain not only abrogated the membrane expression of YAP1 but also significantly increased the levels of nucleic YAP1. As a result, the FAM174A-WWC1 expression increased the oncogenic capacity and invasiveness of normal fibroblasts, which suggests its role as a potential driver mutation of EOCRC.

AB - Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and represents the second most common cause of all cancer-related deaths in Korea. Although epidemiological data indicate a sharp increase in the incidence of CRC among individuals older than 50 years, more than 10% of CRCs occur before reaching 50. These are known as early-onset CRCs (EOCRCs) and are likely to be suggestive of hereditary predisposition. However, known familial CRC syndromes account for only 20% of genetic aberrations of EOCRC, and the remaining 80% are still in question. Therefore, we aimed to establish reproducible biological resources and contribute to expand the mutation database of EOCRC. Four cell lines derived from the original tumor mass of CRC patients diagnosed under age 30 years were established, and next-generation sequencing technique was used to identify the genetic features of EOCRC. We have identified one novel fusion gene, FAM174A-WWC1, and analyzed its functional role. The induction of FAM174A-WWC1 to normal fibroblast caused alternations in cellular morphology as well as intercellular expression of E-cadherin and N-cadherin. Moreover, WWC1 carrying the fused FAM174A domain not only abrogated the membrane expression of YAP1 but also significantly increased the levels of nucleic YAP1. As a result, the FAM174A-WWC1 expression increased the oncogenic capacity and invasiveness of normal fibroblasts, which suggests its role as a potential driver mutation of EOCRC.

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U2 - 10.1016/j.tranon.2019.05.019

DO - 10.1016/j.tranon.2019.05.019

M3 - Article

VL - 12

SP - 1185

EP - 1195

JO - Translational Oncology

JF - Translational Oncology

SN - 1936-5233

IS - 9

ER -