Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer

Determination of frequency and distribution pattern

Humaid O. Al-Shamsi, Jeremy Jones, Yazan Fahmawi, Ibrahim Dahbour, Aziz Tabash, Reham Abdel-Wahab, Ahmed O S Abousamra, Kenna R. Shaw, Lianchun Xiao, Manal M. Hassan, Benjamin R. Kipp, Scott Kopetz, Amr S. Soliman, Robert R. McWilliams, Robert A. Wolff

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in 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 of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC were 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 of KRAS, NRAS, BRAF, PIK3CA, TP53, APC, SMAD, FBXW7 mutations 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 of KRAS, NRAS, BRAF, TP53, APC and PIK3CA mutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency of FBXW7 mutation.

Original languageEnglish (US)
Pages (from-to)882-902
Number of pages21
JournalJournal of Gastrointestinal Oncology
Volume7
Issue number6
DOIs
StatePublished - 2016

Fingerprint

APC Genes
Mutation Rate
Colorectal Neoplasms
Mutation
Population
Mucinous Adenocarcinoma
Neoplasms
Adenocarcinoma

Keywords

  • Arab population
  • Colorectal cancer (CRC)
  • Next-generation sequencing (NGS)
  • Somatic mutations

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

Cite this

Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer : Determination of frequency and distribution pattern. / Al-Shamsi, Humaid O.; Jones, Jeremy; Fahmawi, Yazan; Dahbour, Ibrahim; Tabash, Aziz; Abdel-Wahab, Reham; Abousamra, Ahmed O S; Shaw, Kenna R.; Xiao, Lianchun; Hassan, Manal M.; Kipp, Benjamin R.; Kopetz, Scott; Soliman, Amr S.; McWilliams, Robert R.; Wolff, Robert A.

In: Journal of Gastrointestinal Oncology, Vol. 7, No. 6, 2016, p. 882-902.

Research output: Contribution to journalArticle

Al-Shamsi, HO, Jones, J, Fahmawi, Y, Dahbour, I, Tabash, A, Abdel-Wahab, R, Abousamra, AOS, Shaw, KR, Xiao, L, Hassan, MM, Kipp, BR, Kopetz, S, Soliman, AS, McWilliams, RR & Wolff, RA 2016, 'Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: Determination of frequency and distribution pattern', Journal of Gastrointestinal Oncology, vol. 7, no. 6, pp. 882-902. https://doi.org/10.21037/jgo.2016.11.02
Al-Shamsi, Humaid O. ; Jones, Jeremy ; Fahmawi, Yazan ; Dahbour, Ibrahim ; Tabash, Aziz ; Abdel-Wahab, Reham ; Abousamra, Ahmed O S ; Shaw, Kenna R. ; Xiao, Lianchun ; Hassan, Manal M. ; Kipp, Benjamin R. ; Kopetz, Scott ; Soliman, Amr S. ; McWilliams, Robert R. ; Wolff, Robert A. / Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer : Determination of frequency and distribution pattern. In: Journal of Gastrointestinal Oncology. 2016 ; Vol. 7, No. 6. pp. 882-902.
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title = "Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: Determination of frequency and distribution pattern",
abstract = "Background: The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in 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 of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC were 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 of KRAS, NRAS, BRAF, PIK3CA, TP53, APC, SMAD, FBXW7 mutations 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 of KRAS, NRAS, BRAF, TP53, APC and PIK3CA mutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency of FBXW7 mutation.",
keywords = "Arab population, Colorectal cancer (CRC), Next-generation sequencing (NGS), Somatic mutations",
author = "Al-Shamsi, {Humaid O.} and Jeremy Jones and Yazan Fahmawi and Ibrahim Dahbour and Aziz Tabash and Reham Abdel-Wahab and Abousamra, {Ahmed O S} and Shaw, {Kenna R.} and Lianchun Xiao and Hassan, {Manal M.} and Kipp, {Benjamin R.} and Scott Kopetz and Soliman, {Amr S.} and McWilliams, {Robert R.} and Wolff, {Robert A.}",
year = "2016",
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language = "English (US)",
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TY - JOUR

T1 - Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer

T2 - Determination of frequency and distribution pattern

AU - Al-Shamsi, Humaid O.

AU - Jones, Jeremy

AU - Fahmawi, Yazan

AU - Dahbour, Ibrahim

AU - Tabash, Aziz

AU - Abdel-Wahab, Reham

AU - Abousamra, Ahmed O S

AU - Shaw, Kenna R.

AU - Xiao, Lianchun

AU - Hassan, Manal M.

AU - Kipp, Benjamin R.

AU - Kopetz, Scott

AU - Soliman, Amr S.

AU - McWilliams, Robert R.

AU - Wolff, Robert A.

PY - 2016

Y1 - 2016

N2 - Background: The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in 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 of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC were 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 of KRAS, NRAS, BRAF, PIK3CA, TP53, APC, SMAD, FBXW7 mutations 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 of KRAS, NRAS, BRAF, TP53, APC and PIK3CA mutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency of FBXW7 mutation.

AB - Background: The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in 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 of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC were 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 of KRAS, NRAS, BRAF, PIK3CA, TP53, APC, SMAD, FBXW7 mutations 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 of KRAS, NRAS, BRAF, TP53, APC and PIK3CA mutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency of FBXW7 mutation.

KW - Arab population

KW - Colorectal cancer (CRC)

KW - Next-generation sequencing (NGS)

KW - Somatic mutations

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U2 - 10.21037/jgo.2016.11.02

DO - 10.21037/jgo.2016.11.02

M3 - Article

VL - 7

SP - 882

EP - 902

JO - Journal of Gastrointestinal Oncology

JF - Journal of Gastrointestinal Oncology

SN - 2078-6891

IS - 6

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