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Original research
Somatic deletion of KDM1A/LSD1 gene is associated to advanced colorectal cancer stages
  1. Ruth Ramírez-Ramírez1,
  2. Melva Gutiérrez-Angulo2,3,
  3. Jorge Peregrina-Sandoval1,4,
  4. José Miguel Moreno-Ortiz3,5,
  5. Ramon Antonio Franco-Topete6,7,
  6. Felipe de Jesús Cerda-Camacho8,
  7. Maria de la Luz Ayala-Madrigal3,5
  1. 1 Laboratorio de Inmunología, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Zapopan, México
  2. 2 Departamento de Clínicas, Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitlán de Morelos, México
  3. 3 Programa de Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, México
  4. 4 Laboratorio de Patología Clínica, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Guadalajara, México
  5. 5 Instituto de Genética Humana “Dr. Enrique Corona Rivera”, Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, México
  6. 6 Servicio de Anatomía Patológica, Hospital Civil de Guadalajara "Dr. Juan I Menchaca", Guadalajara, México
  7. 7 Departamento de Microbiología y Patología, Universidad de Guadalajara, Guadalajara, México
  8. 8 Departamento de Anatomía Patológica, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Guadalajara, México
  1. Correspondence to Dr Maria de la Luz Ayala-Madrigal, Instituto de Genética Humana “Dr. Enrique Corona Rivera”, Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, México; luz.ayala{at}academicos.udg.mx

Abstract

Aims KDM1A/LSD1 and ZNF217 are involved in a protein complex that participates in transcriptional regulation. ZNF217 has been analysed in numerous cancers and its amplification has been associated with advanced stages of disease; however, a similar role for KDM1A/LSD1 has not been uncovered. In this study, we estimated the number of KDM1A/LSD1 and ZNF217 gene copies in tissue samples from patients diagnosed with colorectal cancer (CRC), as well as its association with clinicopathological features in patients with CRC.

Methods Paraffin-embedded tumour samples from 50 patients with CRC with a histopathological diagnosis of CRC were included. The number of copies of KDM1A/LSD1 and ZNF217 genes was determined by fluorescence in situ hybridisation (FISH). We also analysed the association between copy numbers of selected genes and clinicopathological data based on multivariate analysis.

Results Deletion of the KDM1A/LSD1 gene occurred in 19 samples (38%), whereas ZNF217 gene amplification was identified in 11 samples (22%). We found a significant association between lymph node metastasis or advanced tumour stage and KDM1A/LSD1 gene deletion (p value=0.0003 and p value=0.011, respectively).

Conclusions KDM1A/LSD1 gene deletion could be considered a novel prognostic biomarker of late-stage CRC.

  • KDM1A/LSD1
  • ZNF217
  • colorectal cancer
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article 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, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/jclinpath-2019-206128

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    Footnotes

    • Handling editor Runjan Chetty.

    • Contributors MLA-M and MG-A conceived and designed the study, RAF-T and FJC-C collected and prepared the samples; RR-R and JP-S performed the experiments. RR-R wrote the paper. MG-A, MLA-M and JMM-O reviewed and edited the manuscript. The final version of the manuscript has been read and approved by all authors.

    • Funding The present study was supported by internal funds of Universidad de Guadalajara.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval This is a cross-sectional and retrospective study approved by the committees of research, ethics and biosecurity, incorporated into the Research State Register 65/UG-JAL/2011. Informed consent was not obtained since the samples corresponded to residual material after pathological diagnosis. The ethics committee approved the material use for scientific research in accordance with the provisions of the ‘International Ethical Guidelines for Health Related Research Involving Humans’, prepared by the Council for International Organizations for Medical Sciences in collaboration with the WHO. The observance of the Mexican General Health Law was also considered. We obtained coded samples before use to maintain absolute confidentiality.

    • Provenance and peer review Not commissioned; internally peer reviewed.

    • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.