Case Report: Cancer spectrum and genetic characteristics of a de novo germline POLD1 p.L606M variant-induced polyposis syndrome
Germline variations in the DNA polymerase genes, POLE and POLD1, can lead to a hereditary cancer syndrome that is characterized by frequent gastrointestinal polyposis and multiple primary malignant tumors. However, because of its rare occurrence, this disorder has not been extensively studied. In th...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1222873/full |
| _version_ | 1797691147589517312 |
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| author | Ying Zhang Xiaolu Wang Yuning Zhu Chong Liang Lijun Zhao Qi Meng Jiani C. Yin Yuqian Shi Fufeng Wang Feng Qin Ji Xuan |
| author_facet | Ying Zhang Xiaolu Wang Yuning Zhu Chong Liang Lijun Zhao Qi Meng Jiani C. Yin Yuqian Shi Fufeng Wang Feng Qin Ji Xuan |
| author_sort | Ying Zhang |
| collection | DOAJ |
| description | Germline variations in the DNA polymerase genes, POLE and POLD1, can lead to a hereditary cancer syndrome that is characterized by frequent gastrointestinal polyposis and multiple primary malignant tumors. However, because of its rare occurrence, this disorder has not been extensively studied. In this report, we present the case of a 22-year-old female patient who had been diagnosed with gastrointestinal polyposis, breast fibroadenoma, multiple primary colorectal cancers, and glioblastoma (grade IV) within a span of 4 years. Next-generation sequencing analysis revealed a germline variant in POLD1 (c.1816C>A; p.L606M). In silico analysis using protein functional predicting software, including SIFT, Polyphen, GERP++, and CADD, further confirmed the pathogenicity of POLD1 p.L606M (classified as ACMG grade Class 4). In line with polymerase deficiency, both rectal cancer and glioblastoma tissues exhibited a high tumor mutation burden, with 16.9 muts/Mb and 347.1 muts/Mb, respectively. Interestingly, the patient has no family history of cancer, and gene examination of both parents confirms that this is a de novo germline variant. Therefore, molecular screening for POLD1 may be necessary for patients with such a cancer spectrum, regardless of their family history. |
| first_indexed | 2024-03-12T02:09:12Z |
| format | Article |
| id | doaj.art-6943fd05bac84e619679c8fa30947a33 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-12T02:09:12Z |
| publishDate | 2023-09-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-6943fd05bac84e619679c8fa30947a332023-09-06T16:26:46ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-09-011310.3389/fonc.2023.12228731222873Case Report: Cancer spectrum and genetic characteristics of a de novo germline POLD1 p.L606M variant-induced polyposis syndromeYing Zhang0Xiaolu Wang1Yuning Zhu2Chong Liang3Lijun Zhao4Qi Meng5Jiani C. Yin6Yuqian Shi7Fufeng Wang8Feng Qin9Ji Xuan10Department of Pathology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, ChinaDepartment of Oncology, The Affiliated Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaDepartment of Pathology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, ChinaDepartment of Neurosurgery Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, ChinaMedical Science Liaison, Genetron Health Inc., Beijing, ChinaGeneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, ChinaGeneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, ChinaGeneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, ChinaGeneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, ChinaCancer Center, Jinling Hospital, Nanjing University School of Medicine, Nanjing, ChinaDepartment of Gastroenterology, Jinling Hospital, Nanjing University, School of Medicine, Nanjing, ChinaGermline variations in the DNA polymerase genes, POLE and POLD1, can lead to a hereditary cancer syndrome that is characterized by frequent gastrointestinal polyposis and multiple primary malignant tumors. However, because of its rare occurrence, this disorder has not been extensively studied. In this report, we present the case of a 22-year-old female patient who had been diagnosed with gastrointestinal polyposis, breast fibroadenoma, multiple primary colorectal cancers, and glioblastoma (grade IV) within a span of 4 years. Next-generation sequencing analysis revealed a germline variant in POLD1 (c.1816C>A; p.L606M). In silico analysis using protein functional predicting software, including SIFT, Polyphen, GERP++, and CADD, further confirmed the pathogenicity of POLD1 p.L606M (classified as ACMG grade Class 4). In line with polymerase deficiency, both rectal cancer and glioblastoma tissues exhibited a high tumor mutation burden, with 16.9 muts/Mb and 347.1 muts/Mb, respectively. Interestingly, the patient has no family history of cancer, and gene examination of both parents confirms that this is a de novo germline variant. Therefore, molecular screening for POLD1 may be necessary for patients with such a cancer spectrum, regardless of their family history.https://www.frontiersin.org/articles/10.3389/fonc.2023.1222873/fullNGSPOLD1POLEgermline POLD1 L606Mpolyposis syndrome |
| spellingShingle | Ying Zhang Xiaolu Wang Yuning Zhu Chong Liang Lijun Zhao Qi Meng Jiani C. Yin Yuqian Shi Fufeng Wang Feng Qin Ji Xuan Case Report: Cancer spectrum and genetic characteristics of a de novo germline POLD1 p.L606M variant-induced polyposis syndrome Frontiers in Oncology NGS POLD1 POLE germline POLD1 L606M polyposis syndrome |
| title | Case Report: Cancer spectrum and genetic characteristics of a de novo germline POLD1 p.L606M variant-induced polyposis syndrome |
| title_full | Case Report: Cancer spectrum and genetic characteristics of a de novo germline POLD1 p.L606M variant-induced polyposis syndrome |
| title_fullStr | Case Report: Cancer spectrum and genetic characteristics of a de novo germline POLD1 p.L606M variant-induced polyposis syndrome |
| title_full_unstemmed | Case Report: Cancer spectrum and genetic characteristics of a de novo germline POLD1 p.L606M variant-induced polyposis syndrome |
| title_short | Case Report: Cancer spectrum and genetic characteristics of a de novo germline POLD1 p.L606M variant-induced polyposis syndrome |
| title_sort | case report cancer spectrum and genetic characteristics of a de novo germline pold1 p l606m variant induced polyposis syndrome |
| topic | NGS POLD1 POLE germline POLD1 L606M polyposis syndrome |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1222873/full |
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