ALK Gene Amplification is Associated with Poor Prognosis in Colorectal Carcinoma

Overview

Journal Br J Cancer

Specialty Oncology

Date 2013 Oct 17

PMID 24129244

Citations 23

Authors

P Bavi

Z Jehan

R Bu

S Prabhakaran

N Al-Sanea

F Al-Dayel

M Al-Assiri

T Al-Halouly

R Sairafi

S Uddin

K S Al-Kuraya

Affiliations

Soon will be listed here.

Abstract

Background: Recently, the anaplastic lymphoma kinase (ALK) has been found to be altered in several solid and haematological tumours. ALK gene copy number changes and mutations in colorectal cancers (CRCs) are not well characterised. We aimed to study the prevalence of ALK copy number changes, translocations, gene mutations and protein expression in 770 CRC patients, and correlate these findings with molecular and clinico-pathological data.

Methods: ALK gene copy number variations and ALK expression were evaluated by fluorescence in situ hybridisation (FISH) and immunohistochemistry, respectively.

Results: Translocations of the ALK gene were not observed; 3.4% (26 out of 756) of the CRC patients tested had an increase in ALK gene copy number either amplification or gain. Interestingly, increased ALK gene copy number alteration was associated with poor prognosis (P=0.0135) and was an independent prognostic marker in multivariate Cox proportional hazards model. The study reveals a significant impact of ALK gene copy number alterations on the outcome of patients with CRC.

Conclusion: The findings of our study highlight a potential role of targeting ALK in advanced CRCs by using ALK FISH and ALK IHC as a screening tool to detect ALK alterations. Based on these findings, a potential role of ALK inhibitor as a therapeutic agent in a subset of CRC merits further investigation.

Citing Articles

ALK fusions in the pan-cancer setting: another tumor-agnostic target?.

Shreenivas A, Janku F, Gouda M, Chen H, George B, Kato S NPJ Precis Oncol. 2023; 7(1):101.

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New perspectives for targeting therapy in ALK-positive human cancers.

Zhao S, Li J, Xia Q, Liu K, Dong Z Oncogene. 2023; 42(24):1959-1969.

PMID: 37149665 DOI: 10.1038/s41388-023-02712-8.

The association of blood ctDNA levels to mutations of marker genes in colorectal cancer.

Bai F, Du Q, Zou Q, Xu L, Dong W, Lv X Cancer Rep (Hoboken). 2023; 6(4):e1782.

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The autocrine loop of ALK receptor and ALKAL2 ligand is an actionable target in consensus molecular subtype 1 colon cancer.

Mazzeschi M, Sgarzi M, Romaniello D, Gelfo V, Cavallo C, Ambrosi F J Exp Clin Cancer Res. 2022; 41(1):113.

PMID: 35351152 PMC: 8962179. DOI: 10.1186/s13046-022-02309-1.

Signet-ring Cell Carcinoma Component as an Indicator of Anaplastic Lymphoma Kinase Mutations in Colorectal Cancer.

Nukada S, Okubo Y, Shiozawa M, Yoshioka E, Suzuki M, Washimi K J Anus Rectum Colon. 2021; 5(2):167-172.

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