Clinical significance of frequent somatic mutations detected by high-throughput targeted sequencing in archived colorectal cancer samples

Journal of Translational Medicine

Research

Mohammed H. Al-Qahtani¹  Abdelbaset Buhmeida¹  Rola Turki²  Jaudah Al-Maghrabi³  Rania Alam⁴  Atlal Abusanad⁵  Shadi Al-Khayyat⁵  Mahmoud Shaheen Al-Ahwal⁶  Huda Banni⁷  Ashraf Dallol⁸  Adel M. Abuzenadah⁹  Osama Bajouh^1,10  Hani A. Alhadrami^1,11  Mohammed Abuzenadah^1,11  Aisha Elaimi^1,11 

[1] Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia;Department of Obstetrics and Gynecology, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia;Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia;Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia;Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia;Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia;Scientific Chair for Colorectal Cancer, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia;KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz University, P.O. Box 80216, 21589, Jeddah, Kingdom of Saudi Arabia;KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz University, P.O. Box 80216, 21589, Jeddah, Kingdom of Saudi Arabia;Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia;KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz University, P.O. Box 80216, 21589, Jeddah, Kingdom of Saudi Arabia;Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia;Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia;KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz University, P.O. Box 80216, 21589, Jeddah, Kingdom of Saudi Arabia;Department of Obstetrics and Gynecology, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia;KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz University, P.O. Box 80216, 21589, Jeddah, Kingdom of Saudi Arabia;Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia;

关键词: Colon cancer;    Next-generation sequencing;    Mutational hotspots;    Somatic;    Hotspots;   

DOI  :  10.1186/s12967-016-0878-9

 received in 2016-03-15, accepted in 2016-04-26,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundColorectal cancer (CRC) is a heterogeneous disease with different molecular characteristics associated with many variables such as the sites from which the tumors originate or the presence or absence of chromosomal instability. Identification of such variables, particularly mutational hotspots, often carries a significant diagnostic and/or prognostic value that could ultimately affect the therapeutic outcome.MethodsHigh-throughput mutational analysis of 99 CRC formalin-fixed and paraffin-embedded (FFPE) cases was performed using the Cancer Hotspots Panel (CHP) v2 on the Ion Torrent™ platform. Correlation with survival and other Clinicopathological parameters was performed using Fisher’s exact test and Kaplan–Meier curve analysis.ResultsTargeted sequencing lead to the identification of frequent mutations in TP53 (65 %), APC (36 %), KRAS (35 %), PIK3CA (19 %), PTEN (13 %), EGFR (11 %), SMAD4 (11 %), and FBXW7 (7 %). Other genes harbored mutations at lower frequency. EGFR mutations were relatively frequent and significantly associated with young age of onset (p = 0.028). Additionally, EGFR or PIK3CA mutations were a marker for poor disease-specific survival in our cohort (p = 0.009 and p = 0.032, respectively). Interestingly, KRAS or PIK3CA mutations were significantly associated with poor disease-specific survival in cases with wild-type TP53 (p = 0.001 and p = 0.02, respectively).ConclusionsFrequent EGFR mutations in this cohort as well as the differential prognostic potential of KRAS and PIK3CA in the presence or absence of detectable TP53 mutations may serve as novel prognostic tools for CRC in patients from the Kingdom of Saudi Arabia. Such findings could help in the clinical decision-making regarding therapeutic intervention for individual patients and provide better diagnosis or prognosis in this locality.

【 授权许可】

CC BY   
© Dallol et al. 2016