Array comparative genomic hybridization based identification of key genetic alterations at 2p21-p16.3 (MSH2, MSH6, EPCAM), 3p23-p14.2 (MLH1), 7p22.1 (PMS2) and 1p34.1-p33 (MUTYH) regions in hereditary non polyposis colorectal cancer (Lynch syndrome) in the Kingdom of Saudi Arabia

Mahmood Rasool; Peter Natesan Pushparaj; Zeenat Mirza; Muhammad Imran Naseer; Heba Abusamra; Maha Alquaiti; Manal Shaabad; Abdulrahman Mohamed Saeed Sibiany; Kalamegam Gauthaman; Mohammed Hussein Al-Qahtani; Sajjad Karim

doi:10.1016/j.sjbs.2019.06.012

Array comparative genomic hybridization based identification of key genetic alterations at 2p21-p16.3 (MSH2, MSH6, EPCAM), 3p23-p14.2 (MLH1), 7p22.1 (PMS2) and 1p34.1-p33 (MUTYH) regions in hereditary non polyposis colorectal cancer (Lynch syndrome) in the Kingdom of Saudi Arabia

Saudi J Biol Sci. 2020 Jan;27(1):157-162. doi: 10.1016/j.sjbs.2019.06.012. Epub 2019 Jun 15.

Authors

Mahmood Rasool^{1

2}, Peter Natesan Pushparaj^{1

2}, Zeenat Mirza^{3

2}, Muhammad Imran Naseer^{1

2}, Heba Abusamra¹, Maha Alquaiti¹, Manal Shaabad¹, Abdulrahman Mohamed Saeed Sibiany⁴, Kalamegam Gauthaman^{1

2}, Mohammed Hussein Al-Qahtani^{1

2}, Sajjad Karim^{1

2}

Affiliations

¹ Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
² Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
³ King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
⁴ Deptartment of Surgery, Faculty of Medicine, KAUH, King Abdulaziz University, Jeddah, Saudi Arabia.

Abstract

Lynch syndrome is inherited in an autosomal dominant mode. Lynch syndrome is caused by impairment of one or more of the various genes (most frequently MLH1 and MSH2) involved in mismatch repair. In this study, whole genome comparative genomic hybridization array (array CGH) based genomic analysis was performed on twelve Saudi Lynch syndrome patients. A total of 124 chromosomal alterations (structural loss) were identified at mean log2 ratio cut off value of ±0.25. We also found structural loss in 2p21-p16.3, 3p23-p14.2, 7p22.1 and 1p34.1-p33 regions. These findings were subsequently validated by real time quantitative PCR showing downregulation of MSH2, MSH6, EPCAM, MLH1, PMS2 and MUTYH genes. These findings shall help in establishing database for alterations in mismatch repair genes underlying Lynch syndrome in Saudi population as well as to determine the incidence ratio of these disorders. Guided counselling will subsequently lead to the prevention and eradication of Lynch Syndrome in the local population.

Keywords: Familial colorectal cancer; Lynch syndrome; Mismatch repair genes; arrayCGH.