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.

Related Articles

Alfredo V Chua Jr, Alvin Christopher S Chu, Ashraf A Tawasil, Michael D San Juan
Divya Bala Thumaty, Titus Chacko Raju, Oommen John Ajoy, Anjana Joel, Josh Thomas Georgy, Myla Jacob, Inian Samarasam, Dipti Masih, Rajesh Isaiah, Visalakshi Jeyaseelan, Ashish Singh
Shridevi Subramaniam, Yek-Ching Kong, Hafizah Zaharah, Cuno SPM Uiterwaal, Andrea Richard, Nur Aishah Taib, Azura Deniel, Kok-Han Chee, Ros Suzanna Bustamam, Mee-Hoong See, Alan Fong, Cheng-Har Yip, Nirmala Bhoo-Pathy
Tapesh Bhattacharyya, Moses Arunsingh, Santam Chakraborty, Vishnu Harilal, Rohit Sasidharan, Saheli Saha, Robin Thambudorai, Bipradas Roy, Sudeep Banerjee, Paromita Roy, Soumendranath Ray, Indranil Mallick
Jeel Moya-Salazar, Eulogio Cáceres, Jorgelina Blejer, Carlos Gonzalez, Hans Contreras-Pulache