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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Identification of IL11RA and MELK amplification in gastric cancer by comprehensive genomic profiling of gastric cancer cell lines
Danielle Queiroz Calcagno, Sylvia Santomi Takeno, Carolina Oliveira Gigek, Mariana Ferreira Leal, Fernanda Wisnieski, Elizabeth Suchi Chen, Taíssa Maíra Thomaz Araújo, Eleonidas Moura Lima, Maria Isabel Melaragno, Samia Demachki, Paulo Pimentel Assumpção, Rommel Rodriguez Burbano, Marília Cardoso Smith
Danielle Queiroz Calcagno, Sylvia Santomi Takeno, Carolina Oliveira Gigek, Mariana Ferreira Leal, Fernanda Wisnieski, Elizabeth Suchi Chen, Maria Isabel Melaragno, Marília Cardoso Smith, Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, SP 04021-001, Brazil
Danielle Queiroz Calcagno, Taíssa Maíra Thomaz Araújo, Samia Demachki, Paulo Pimentel Assumpção, Rommel Rodriguez Burbano, Núcleo de Pesquisas em Oncologia, Hospital Universitário João de Barros Barreto, Belém, PA 66073-000, Brazil
Sylvia Santomi Takeno, Eleonidas Moura Lima, Departamento de Biologia Molecular, Universidade Federal da Paraíba, João Pessoa, PB 58051-900, Brazil
Carolina Oliveira Gigek, Disciplina de Gastroenterologia Cirúrgica, Universidade Federal de São Paulo, São Paulo, SP 04021-001, Brazil
Mariana Ferreira Leal, Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo, São Paulo, SP 04021-001, Brazil
Author contributions: Calcagno DQ and Takeno SS performed the majority of experiments and analyzed the data; Gigek CO, Leal MF, Wisnieski F, Chen ES and Araújo TMT performed aCGH investigations; Lima EM performed samples collect; Demachki S made tumor microdissection; Melaragno MI, Burbano RR and Smith MC designed and coordinated the research; Calcagno DQ wrote the paper; Leal MF, Wisnieski F and Assumpção PP reviewed the paper critically.
Supported by Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP, No. 2009/07145-9.
Institutional review board statement: All specimens were taken after informed consente and ethical permission was obtained for participation in the study. The study was reviewed and approved by the HUJBB Institutional Review Board.
Conflict-of-interest statement: The authors declare that there is no conflict of interests regarding the publication of this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Danielle Queiroz Calcagno, PhD, Núcleo de Pesquisas em Oncologia, Hospital Universitário João de Barros Barreto, Av. Mundurucus, 4487, 1º Piso da Unacon, Belém, PA 66073-000, Brazil.
danicalcagno@gmail.com
Telephone: +55-91-32016776
Received: July 15, 2016
Peer-review started: July 16, 2016
First decision: August 19, 2016
Revised: September 10, 2016
Accepted: October 10, 2016
Article in press: October 10, 2016
Published online: November 21, 2016
Processing time: 126 Days and 12.1 Hours
AIM
To identify common copy number alterations on gastric cancer cell lines.
METHODS
Four gastric cancer cell lines (ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR analysis.
RESULTS
The amplification of 9p13.3 was detected in all cell lines by both methodologies. An increase in the copy number of 9p13.3 was also confirmed by fluorescence in situ hybridization analysis. Moreover, the interleukin 11 receptor alpha (IL11RA) and maternal embryonic leucine zipper kinase (MELK) genes, which are present in the 9p13.3 amplicon, revealed gains of the MELK gene in all the cell lines studied. Additionally, a gain in the copy number of IL11RA and MELK was observed in 19.1% (13/68) and 55.9% (38/68) of primary gastric adenocarcinoma samples, respectively.
CONCLUSION
The characterization of a small gain region at 9p13.3 in gastric cancer cell lines and primary gastric adenocarcinoma samples has revealed MELK as a candidate target gene that is possibly related to the development of gastric cancer.
Core tip: While the presence of alterations in the DNA copy number is one of the key hallmarks of carcinogenesis, in gastric cancer, the chromosomal regions with frequent gain and loss are still poorly defined. Array comparative genome hybridization is a high resolution tool that allows the simultaneous detection of sub-microscopic copy number changes across the genome. The characterization of a small gain or loss region in gastric cancer cell lines and primary gastric adenocarcinoma samples could reveal a candidate target gene that may possibly be linked to the development of gastric cancer.
