Genomic analysis of a Palestinian family with inherited cancer syndrome: a next-generation sequencing study
Familial predisposition is a strong risk factor for different types of cancer and accounts for around 10% of the cases. In this study, we investigated cancer predisposition in a Palestinian family using whole-exome sequencing (WES) technologies. In this study, we focused more on cutaneous melanoma (...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1230241/full |
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| author | Eman Fares Rua Thawabtah Husam Sallam Areej A. H. Khatib Nouar Qutob Zaidoun Salah |
| author_facet | Eman Fares Rua Thawabtah Husam Sallam Areej A. H. Khatib Nouar Qutob Zaidoun Salah |
| author_sort | Eman Fares |
| collection | DOAJ |
| description | Familial predisposition is a strong risk factor for different types of cancer and accounts for around 10% of the cases. In this study, we investigated cancer predisposition in a Palestinian family using whole-exome sequencing (WES) technologies. In this study, we focused more on cutaneous melanoma (CM). Our analysis identified three heterozygous rare missense variants, WRN (p.L383F and p.A995T) and TYRP1 (p.T262M) and a pathogenic homozygous missense mutation in ERCC2 (p.R683Q). Although WRN and TYRP1 genes and their variations were correlated with different types of cancer, including melanoma, the currently identified WRN and TYRP1 variants were not reported previously in melanoma cases. The pathogenic mutation was segregated with the clinical phenotypes and found in the two affected brothers, one with CM and the other with brain tumor, and was confirmed by Sanger sequencing analysis. Segregation analysis of this mutation revealed that family members are either heterozygous or wild type. Our findings confirm that the homozygous ERCC2 (p.R683Q) mutation was responsible for causing melanoma and other cancer types in the family. Our work highlights the value to decipher the mutational background of familial cancers, especially CM, in the Palestinian population to guide diagnosis, prevention, and treatment of affected patients and their families. |
| first_indexed | 2024-03-11T14:33:42Z |
| format | Article |
| id | doaj.art-d38c2561c01f49c3a70a3844919e4bc4 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-11T14:33:42Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-d38c2561c01f49c3a70a3844919e4bc42023-10-31T05:49:59ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-10-011410.3389/fgene.2023.12302411230241Genomic analysis of a Palestinian family with inherited cancer syndrome: a next-generation sequencing studyEman Fares0Rua Thawabtah1Husam Sallam2Areej A. H. Khatib3Nouar QutobZaidoun SalahHealth Sciences Department, Faculty of Graduate Studies, Arab American University, Ramallah, PalestineHealth Sciences Department, Faculty of Graduate Studies, Arab American University, Ramallah, PalestineHealth Sciences Department, Faculty of Graduate Studies, Arab American University, Ramallah, PalestineWomen Health Research Unit, McGill University Health Center, Montreal, QC, CanadaFamilial predisposition is a strong risk factor for different types of cancer and accounts for around 10% of the cases. In this study, we investigated cancer predisposition in a Palestinian family using whole-exome sequencing (WES) technologies. In this study, we focused more on cutaneous melanoma (CM). Our analysis identified three heterozygous rare missense variants, WRN (p.L383F and p.A995T) and TYRP1 (p.T262M) and a pathogenic homozygous missense mutation in ERCC2 (p.R683Q). Although WRN and TYRP1 genes and their variations were correlated with different types of cancer, including melanoma, the currently identified WRN and TYRP1 variants were not reported previously in melanoma cases. The pathogenic mutation was segregated with the clinical phenotypes and found in the two affected brothers, one with CM and the other with brain tumor, and was confirmed by Sanger sequencing analysis. Segregation analysis of this mutation revealed that family members are either heterozygous or wild type. Our findings confirm that the homozygous ERCC2 (p.R683Q) mutation was responsible for causing melanoma and other cancer types in the family. Our work highlights the value to decipher the mutational background of familial cancers, especially CM, in the Palestinian population to guide diagnosis, prevention, and treatment of affected patients and their families.https://www.frontiersin.org/articles/10.3389/fgene.2023.1230241/fullcutaneous melanoma, xeroderma pigmentosumNERPalestinian familyERCC2/XPDcancer syndrome |
| spellingShingle | Eman Fares Rua Thawabtah Husam Sallam Areej A. H. Khatib Nouar Qutob Zaidoun Salah Genomic analysis of a Palestinian family with inherited cancer syndrome: a next-generation sequencing study Frontiers in Genetics cutaneous melanoma, xeroderma pigmentosum NER Palestinian family ERCC2/XPD cancer syndrome |
| title | Genomic analysis of a Palestinian family with inherited cancer syndrome: a next-generation sequencing study |
| title_full | Genomic analysis of a Palestinian family with inherited cancer syndrome: a next-generation sequencing study |
| title_fullStr | Genomic analysis of a Palestinian family with inherited cancer syndrome: a next-generation sequencing study |
| title_full_unstemmed | Genomic analysis of a Palestinian family with inherited cancer syndrome: a next-generation sequencing study |
| title_short | Genomic analysis of a Palestinian family with inherited cancer syndrome: a next-generation sequencing study |
| title_sort | genomic analysis of a palestinian family with inherited cancer syndrome a next generation sequencing study |
| topic | cutaneous melanoma, xeroderma pigmentosum NER Palestinian family ERCC2/XPD cancer syndrome |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1230241/full |
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