ecancermedicalscience

Clinical Study

Computational analyses on genetic alterations in the NSD genes family and the implications for colorectal cancer development

15 Jan 2020
Vívian D'Afonseca, Glória Gónzalez, Marcela Salazar, Ariel D Arencibia

Colorectal cancer (CRC) is a prevalent tumour throughout the world. CRC symptoms appear only in advanced stages causing decrease in survival of patients. Therefore, it is necessary to establish new strategies to detect CRC through subclinical screening. Genetic alterations and differential expression of genes that codify histone methyltransferases (HMTs) are linked to tumourigenesis of CRC. One important group of genes that codify HMTs are the NSD family composed of NSD1, NSD2 and NSD3 genes. This family participates in several cancer processes as oncogenes, harbouring several genetic alterations and presenting differential expression in tumour cells. To investigate the implications of NSD genes in CRC cancer, we described the genomic landscape of all NSD family members in a cohort of CRC patients from publicly available cancer datasets. We identified associations among recurrent copy number alterations (CNAs), mutations and differential gene expression concerning clinical outcome. We found in CRC repositories that NSD1 harbours a missense mutation in SET domain—the catalytic region—that probably could decrease its activity. In addition, we found an association between the low expressions of NSD1 and NSD2 and decrease of survival probability in CRC patients. Finally, we reported that NSD3 showed the highest rate of gene amplification, which was highly correlated to its mRNA expression, a common feature of many cancer drivers. Our results highlight the potential use of the NSD1 and NSD2 gene as prognostic markers of poor prognosis in CRC patients. Additionally, we appointed the use of the NSD3 gene as a putative cancer driver gene in CRC given that this gene harbours the highest rate of genetic amplification. All our findings are leading to novel strategies to predict and control CRC, however, some studies need to be conducted to validate these findings.

Article metrics: 488 views
312
176

Related Articles

Patricia Rioja, Guillermo Valencia, César Centurión-Rodriguez, Zaida Morante, Mercedes Bravo, Lourdes Huanca, Carlos Morante
Gunjesh Kumar Singh, Hollis DSouza, Nandini Menon, Sujay Srinivas, Dilip Harindran Vallathol, Mounika Boppana, Annu Rajpurohit, Abhishek Mahajan, Amit Janu, Abhishek Chatterjee, Rahul Krishnatry, Tejpal Gupta, Rakesh Jalali, Vijay M Patil
Luis Villanueva, Jaime Anabalón, Jean M Butte, Pamela Salman, Sergio Panay, Elizabeth Milla, Carlos Gallardo, Sebastian Hoefler, Roberto Charles, Felipe Reyes, Olga Barajas, Luis Matamala, Angelica Molina, Sergio Portiño, Marcela Berrios, Christian Caglevic, Mauricio Mahave