POLE and POLD1 germline exonuclease domain pathogenic variants, a rare event in colorectal cancer from the Middle East

Molecular Genetics & Genomic Medicine

Alaa Abduljabbar¹  Luai H. Ashari¹  Fouad Al‐Dayel²  Maham Arshad³  Khadija A. S. Al‐Obaisi³  Sandeep K. Parvathareddy³  Maha Al‐Rasheed³  Abdul K. Siraj³  Yan Kong³  Khawla S. Al‐Kuraya³  Nabil Siraj³  Rong Bu³  Kaleem Iqbal³  Tariq Masoodi³  Ingrid G. Victoria³  Saeeda O. Ahmed³ 

[1] Colorectal Section Department of Surgery King Faisal Specialist Hospital and Research Center Riyadh Saudi Arabia;Department of Pathology and Laboratory Medicine King Faisal Specialist Hospital and Research Center Riyadh Saudi Arabia;Human Cancer Genomic Research Research Center King Faisal Specialist Hospital and Research Center iyadh Saudi Arabia;

关键词: colorectal cancers;    Middle East;    POLD1;    POLE;    variant;   

DOI  :  10.1002/mgg3.1368

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown