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POLE and POLD1 germline exonuclease domain pathogenic variants, a rare event in colorectal cancer from the Middle East.
Siraj, Abdul K; Bu, Rong; Iqbal, Kaleem; Parvathareddy, Sandeep K; Masoodi, Tariq; Siraj, Nabil; Al-Rasheed, Maha; Kong, Yan; Ahmed, Saeeda O; Al-Obaisi, Khadija A S; Victoria, Ingrid G; Arshad, Maham; Al-Dayel, Fouad; Abduljabbar, Alaa; Ashari, Luai H; Al-Kuraya, Khawla S.
Affiliation
  • Siraj AK; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, iyadh, Saudi Arabia.
  • Bu R; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, iyadh, Saudi Arabia.
  • Iqbal K; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, iyadh, Saudi Arabia.
  • Parvathareddy SK; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, iyadh, Saudi Arabia.
  • Masoodi T; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, iyadh, Saudi Arabia.
  • Siraj N; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, iyadh, Saudi Arabia.
  • Al-Rasheed M; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, iyadh, Saudi Arabia.
  • Kong Y; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, iyadh, Saudi Arabia.
  • Ahmed SO; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, iyadh, Saudi Arabia.
  • Al-Obaisi KAS; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, iyadh, Saudi Arabia.
  • Victoria IG; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, iyadh, Saudi Arabia.
  • Arshad M; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, iyadh, Saudi Arabia.
  • Al-Dayel F; Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
  • Abduljabbar A; Colorectal Section, Department of Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
  • Ashari LH; Colorectal Section, Department of Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
  • Al-Kuraya KS; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, iyadh, Saudi Arabia.
Mol Genet Genomic Med ; 8(8): e1368, 2020 08.
Article in En | MEDLINE | ID: mdl-32567205
ABSTRACT

BACKGROUND:

Colorectal cancer (CRC) is a major contributor to morbidity and mortality related to cancer. Only ~5% of all CRCs occur as a result of pathogenic variants in well-defined CRC predisposing genes. The frequency and effect of exonuclease domain pathogenic variants of POLE and POLD1 genes in Middle Eastern CRCs is still unknown.

METHODS:

Targeted capture sequencing and Sanger sequencing technologies were employed to investigate the germline exonuclease domain pathogenic variants of POLE and POLD1 in Middle Eastern CRCs. Immunohistochemical analysis of POLE and POLD1 was performed to look for associations between protein expression and clinico-pathological characteristics.

RESULTS:

Five damaging or possibly damaging variants (0.44%) were detected in 1,135 CRC cases, four in POLE gene (0.35%, 4/1,135) and one (0.1%, 1/1,135) in POLD1 gene. Furthermore, low POLE protein expression was identified in 38.9% (417/1071) cases and a significant association with lymph node involvement (p = .0184) and grade 3 tumors (p = .0139) was observed. Whereas, low POLD1 expression was observed in 51.9% (555/1069) of cases and was significantly associated with adenocarcinoma histology (p = .0164), larger tumor size (T3 and T4 tumors; p = .0012), and stage III tumors (p = .0341).

CONCLUSION:

POLE and POLD1 exonuclease domain pathogenic variants frequency in CRC cases was very low and these exonuclease domain pathogenic variants might be rare causative events of CRC in the Middle East. POLE and POLD1 can be included in multi-gene panels to screen CRC patients.
Subject(s)
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Germ-Line Mutation / DNA Polymerase II / DNA Polymerase III / Poly-ADP-Ribose Binding Proteins Type of study: Prognostic_studies Limits: Aged / Female / Humans / Male / Middle aged Country/Region as subject: Asia Language: En Journal: Mol Genet Genomic Med Year: 2020 Document type: Article Affiliation country: Arabia Saudita

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Germ-Line Mutation / DNA Polymerase II / DNA Polymerase III / Poly-ADP-Ribose Binding Proteins Type of study: Prognostic_studies Limits: Aged / Female / Humans / Male / Middle aged Country/Region as subject: Asia Language: En Journal: Mol Genet Genomic Med Year: 2020 Document type: Article Affiliation country: Arabia Saudita