title: Molecular spectrum ofKRAS,NRAS,BRAF,PIK3CA,TP53, andAPCsomatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern.
abstract: BACKGROUND
  The frequency rates of mutations such asKRAS, NRAS, BRAF,andPIK3CAin colorectal cancer (CRC) differ among populations. The aim of this study was to assess mutation frequencies in the Arab population and determine their correlations with certain clinicopathological features.
  
  
  METHODS
  Arab patients from the Arab Gulf region and a population of age- and sex-matched Western patients with CRC whose tumors were evaluated with next-generation sequencing (NGS) were identified and retrospectively reviewed. The mutation rates ofKRAS, NRAS, BRAF, PIK3CA, TP53,andAPCwere recorded, along with clinicopathological features. Other somatic mutation and their rates were also identified. Fisher's exact test was used to determine the association between mutation status and clinical features.
  
  
  RESULTS
  A total of 198 cases were identified; 99 Arab patients and 99 Western patients. Fifty-two point seven percent of Arab patients had stage IV disease at initial presentation, 74.2% had left-sided tumors. Eighty-nine point two percent had tubular adenocarcinoma and 10.8% had mucinous adenocarcinoma. The prevalence rates ofKRAS, NRAS, BRAF, PIK3CA, TP53, APC, SMAD, FBXW7mutations in Arab population were 44.4%, 4%, 4%, 13.1%, 52.5%, 27.3%, 2% and 3% respectively. Compared to 48.4%, 4%, 4%, 12.1%, 47.5%, 24.2%, 11.1% and 0% respectively in matched Western population. Associations between these mutations and patient clinicopathological features were not statistically significant.
  
  
  CONCLUSIONS
  This is the first study to report comprehensive hotspot mutations using NGS in Arab patients with CRC. The frequency ofKRAS, NRAS, BRAF, TP53, APCandPIK3CAmutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency ofFBXW7mutation.
authors.affiliation: Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA;; Khalifa Bin Zayed Al Nahyan Foundation, Abu Dhabi, United Arab Emirates;; Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Humaid O
authors.initials: HO
authors.lastname: Al-Shamsi
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Jones
authors.affiliation: Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Yazan
authors.initials: Y
authors.lastname: Fahmawi
authors.affiliation: Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Dahbour
authors.affiliation: Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Aziz
authors.initials: A
authors.lastname: Tabash
authors.affiliation: Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA;; Clinical Oncology Department, Assiut University, Assiut, Egypt.
authors.forename: Reham
authors.initials: R
authors.lastname: Abdel-Wahab
authors.affiliation: Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ahmed O S
authors.initials: AO
authors.lastname: Abousamra
authors.affiliation: Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Kenna R
authors.initials: KR
authors.lastname: Shaw
authors.affiliation: Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Lianchun
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Manal M
authors.initials: MM
authors.lastname: Hassan
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Kipp
authors.affiliation: Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Kopetz
authors.affiliation: Department of Epidemiology, the University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Amr S
authors.initials: AS
authors.lastname: Soliman
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: McWilliams
authors.affiliation: Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
keywords: Arab population; Somatic mutations; colorectal cancer (CRC); next-generation sequencing (NGS)