POLE and POLD1 germline exonuclease domain pathogenic variants, a rare event in colorectal cancer from the Middle East
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...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-08-01
|
| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.1368 |
| _version_ | 1797301079761747968 |
|---|---|
| author | Abdul K. Siraj Rong Bu Kaleem Iqbal Sandeep K. Parvathareddy Tariq Masoodi Nabil Siraj Maha Al‐Rasheed Yan Kong Saeeda O. Ahmed Khadija A. S. Al‐Obaisi Ingrid G. Victoria Maham Arshad Fouad Al‐Dayel Alaa Abduljabbar Luai H. Ashari Khawla S. Al‐Kuraya |
| author_facet | Abdul K. Siraj Rong Bu Kaleem Iqbal Sandeep K. Parvathareddy Tariq Masoodi Nabil Siraj Maha Al‐Rasheed Yan Kong Saeeda O. Ahmed Khadija A. S. Al‐Obaisi Ingrid G. Victoria Maham Arshad Fouad Al‐Dayel Alaa Abduljabbar Luai H. Ashari Khawla S. Al‐Kuraya |
| author_sort | Abdul K. Siraj |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T23:16:15Z |
| format | Article |
| id | doaj.art-b914458beafd4f359c0dd5f329bbe6c5 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:16:15Z |
| publishDate | 2020-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-b914458beafd4f359c0dd5f329bbe6c52024-02-21T11:08:50ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-08-0188n/an/a10.1002/mgg3.1368POLE and POLD1 germline exonuclease domain pathogenic variants, a rare event in colorectal cancer from the Middle EastAbdul K. Siraj0Rong Bu1Kaleem Iqbal2Sandeep K. Parvathareddy3Tariq Masoodi4Nabil Siraj5Maha Al‐Rasheed6Yan Kong7Saeeda O. Ahmed8Khadija A. S. Al‐Obaisi9Ingrid G. Victoria10Maham Arshad11Fouad Al‐Dayel12Alaa Abduljabbar13Luai H. Ashari14Khawla S. Al‐Kuraya15Human Cancer Genomic Research Research Center King Faisal Specialist Hospital and Research Center iyadh Saudi ArabiaHuman Cancer Genomic Research Research Center King Faisal Specialist Hospital and Research Center iyadh Saudi ArabiaHuman Cancer Genomic Research Research Center King Faisal Specialist Hospital and Research Center iyadh Saudi ArabiaHuman Cancer Genomic Research Research Center King Faisal Specialist Hospital and Research Center iyadh Saudi ArabiaHuman Cancer Genomic Research Research Center King Faisal Specialist Hospital and Research Center iyadh Saudi ArabiaHuman Cancer Genomic Research Research Center King Faisal Specialist Hospital and Research Center iyadh Saudi ArabiaHuman Cancer Genomic Research Research Center King Faisal Specialist Hospital and Research Center iyadh Saudi ArabiaHuman Cancer Genomic Research Research Center King Faisal Specialist Hospital and Research Center iyadh Saudi ArabiaHuman Cancer Genomic Research Research Center King Faisal Specialist Hospital and Research Center iyadh Saudi ArabiaHuman Cancer Genomic Research Research Center King Faisal Specialist Hospital and Research Center iyadh Saudi ArabiaHuman Cancer Genomic Research Research Center King Faisal Specialist Hospital and Research Center iyadh Saudi ArabiaHuman Cancer Genomic Research Research Center King Faisal Specialist Hospital and Research Center iyadh Saudi ArabiaDepartment of Pathology and Laboratory Medicine King Faisal Specialist Hospital and Research Center Riyadh Saudi ArabiaColorectal Section Department of Surgery King Faisal Specialist Hospital and Research Center Riyadh Saudi ArabiaColorectal Section Department of Surgery King Faisal Specialist Hospital and Research Center Riyadh Saudi ArabiaHuman Cancer Genomic Research Research Center King Faisal Specialist Hospital and Research Center iyadh Saudi ArabiaAbstract 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.https://doi.org/10.1002/mgg3.1368colorectal cancersMiddle EastPOLD1POLEvariant |
| spellingShingle | Abdul K. Siraj Rong Bu Kaleem Iqbal Sandeep K. Parvathareddy Tariq Masoodi Nabil Siraj Maha Al‐Rasheed Yan Kong Saeeda O. Ahmed Khadija A. S. Al‐Obaisi Ingrid G. Victoria Maham Arshad Fouad Al‐Dayel Alaa Abduljabbar Luai H. Ashari Khawla S. Al‐Kuraya POLE and POLD1 germline exonuclease domain pathogenic variants, a rare event in colorectal cancer from the Middle East Molecular Genetics & Genomic Medicine colorectal cancers Middle East POLD1 POLE variant |
| title | POLE and POLD1 germline exonuclease domain pathogenic variants, a rare event in colorectal cancer from the Middle East |
| title_full | POLE and POLD1 germline exonuclease domain pathogenic variants, a rare event in colorectal cancer from the Middle East |
| title_fullStr | POLE and POLD1 germline exonuclease domain pathogenic variants, a rare event in colorectal cancer from the Middle East |
| title_full_unstemmed | POLE and POLD1 germline exonuclease domain pathogenic variants, a rare event in colorectal cancer from the Middle East |
| title_short | POLE and POLD1 germline exonuclease domain pathogenic variants, a rare event in colorectal cancer from the Middle East |
| title_sort | pole and pold1 germline exonuclease domain pathogenic variants a rare event in colorectal cancer from the middle east |
| topic | colorectal cancers Middle East POLD1 POLE variant |
| url | https://doi.org/10.1002/mgg3.1368 |
| work_keys_str_mv | AT abdulksiraj poleandpold1germlineexonucleasedomainpathogenicvariantsarareeventincolorectalcancerfromthemiddleeast AT rongbu poleandpold1germlineexonucleasedomainpathogenicvariantsarareeventincolorectalcancerfromthemiddleeast AT kaleemiqbal poleandpold1germlineexonucleasedomainpathogenicvariantsarareeventincolorectalcancerfromthemiddleeast AT sandeepkparvathareddy poleandpold1germlineexonucleasedomainpathogenicvariantsarareeventincolorectalcancerfromthemiddleeast AT tariqmasoodi poleandpold1germlineexonucleasedomainpathogenicvariantsarareeventincolorectalcancerfromthemiddleeast AT nabilsiraj poleandpold1germlineexonucleasedomainpathogenicvariantsarareeventincolorectalcancerfromthemiddleeast AT mahaalrasheed poleandpold1germlineexonucleasedomainpathogenicvariantsarareeventincolorectalcancerfromthemiddleeast AT yankong poleandpold1germlineexonucleasedomainpathogenicvariantsarareeventincolorectalcancerfromthemiddleeast AT saeedaoahmed poleandpold1germlineexonucleasedomainpathogenicvariantsarareeventincolorectalcancerfromthemiddleeast AT khadijaasalobaisi poleandpold1germlineexonucleasedomainpathogenicvariantsarareeventincolorectalcancerfromthemiddleeast AT ingridgvictoria poleandpold1germlineexonucleasedomainpathogenicvariantsarareeventincolorectalcancerfromthemiddleeast AT mahamarshad poleandpold1germlineexonucleasedomainpathogenicvariantsarareeventincolorectalcancerfromthemiddleeast AT fouadaldayel poleandpold1germlineexonucleasedomainpathogenicvariantsarareeventincolorectalcancerfromthemiddleeast AT alaaabduljabbar poleandpold1germlineexonucleasedomainpathogenicvariantsarareeventincolorectalcancerfromthemiddleeast AT luaihashari poleandpold1germlineexonucleasedomainpathogenicvariantsarareeventincolorectalcancerfromthemiddleeast AT khawlasalkuraya poleandpold1germlineexonucleasedomainpathogenicvariantsarareeventincolorectalcancerfromthemiddleeast |