Novel Candidate <i>loci</i> and Pathogenic Germline Variants Involved in Familial Hematological Malignancies Revealed by Whole-Exome Sequencing
The familial occurrence of hematological malignancies has been underappreciated. Recent studies suggest that up to 15% of adults with myeloid neoplasms carry germline pathogenic variants in cancer-predisposing genes. This study aimed to identify the underlying germline predisposition variant in pati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/3/944 |
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| author | Cristina Andrés-Zayas Julia Suárez-González María Chicano-Lavilla Mariana Bastos Oreiro Gabriela Rodríguez-Macías Patricia Font López Santiago Osorio Prendes Gillen Oarbeascoa Royuela Patricia García Ramírez Rocío Nieves Salgado Ignacio Gómez-Centurión Diego Carbonell Muñoz Paula Muñiz Mi Kwon José Luis Díez-Martín Ismael Buño Carolina Martínez-Laperche |
| author_facet | Cristina Andrés-Zayas Julia Suárez-González María Chicano-Lavilla Mariana Bastos Oreiro Gabriela Rodríguez-Macías Patricia Font López Santiago Osorio Prendes Gillen Oarbeascoa Royuela Patricia García Ramírez Rocío Nieves Salgado Ignacio Gómez-Centurión Diego Carbonell Muñoz Paula Muñiz Mi Kwon José Luis Díez-Martín Ismael Buño Carolina Martínez-Laperche |
| author_sort | Cristina Andrés-Zayas |
| collection | DOAJ |
| description | The familial occurrence of hematological malignancies has been underappreciated. Recent studies suggest that up to 15% of adults with myeloid neoplasms carry germline pathogenic variants in cancer-predisposing genes. This study aimed to identify the underlying germline predisposition variant in patients with a strong family or personal onco-hematological history using whole exome sequencing on sixteen uncharacterized individuals. It was carried out in two groups of patients, one with samples available from two affected relatives (Cohort A) and one with available samples from the index case (Cohort B). In Cohort A, six families were characterized. Two families shared variants in genes associated with DNA damage response and involved in cancer development (<i>CHEK2</i> and <i>RAD54L</i>). Pathogenic or likely pathogenic germline variants were also found in novel candidate genes (<i>NFATC2</i> and <i>TC2N</i>). In two families, any relevant pathogenic or likely pathogenic genomic variants were identified. In Cohort B, four additional index cases were analyzed. Three of them harbor clinically relevant variants in genes with a probable role in the development of inherited forms of hematological malignancies (<i>GATA1</i>, <i>MSH4</i> and <i>PRF1</i>). Overall, whole exome sequencing is a useful approach to achieve a further characterization of these patients and their mutational spectra. Moreover, further investigations may help improve optimization for disease management of affected patients and their families. |
| first_indexed | 2024-03-11T09:49:43Z |
| format | Article |
| id | doaj.art-07220a09b616478199925ae2643143c1 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T09:49:43Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-07220a09b616478199925ae2643143c12023-11-16T16:19:28ZengMDPI AGCancers2072-66942023-02-0115394410.3390/cancers15030944Novel Candidate <i>loci</i> and Pathogenic Germline Variants Involved in Familial Hematological Malignancies Revealed by Whole-Exome SequencingCristina Andrés-Zayas0Julia Suárez-González1María Chicano-Lavilla2Mariana Bastos Oreiro3Gabriela Rodríguez-Macías4Patricia Font López5Santiago Osorio Prendes6Gillen Oarbeascoa Royuela7Patricia García Ramírez8Rocío Nieves Salgado9Ignacio Gómez-Centurión10Diego Carbonell Muñoz11Paula Muñiz12Mi Kwon13José Luis Díez-Martín14Ismael Buño15Carolina Martínez-Laperche16Genomics Unit, Gregorio Marañón General University Hospital, Gregorio Marañón Health Research Institute (IiSGM), 28009 Madrid, SpainGenomics Unit, Gregorio Marañón General University Hospital, Gregorio Marañón Health Research Institute (IiSGM), 28009 Madrid, SpainGregorio Marañón Health Research Institute (IiSGM), 28009 Madrid, SpainGregorio Marañón Health Research Institute (IiSGM), 28009 Madrid, SpainDepartment of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, SpainDepartment of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, SpainDepartment of Hematology, Gregorio Marañón General University Hospital, 28007 Madrid, SpainGregorio Marañón Health Research Institute (IiSGM), 28009 Madrid, SpainDepartment of Hematology, Hospital Universitario Príncipe de Asturias, 28802 Madrid, SpainDepartment of Hematology, Hospital Universitario Fundación Jiménez Díaz, 28040 Madrid, SpainGregorio Marañón Health Research Institute (IiSGM), 28009 Madrid, SpainGregorio Marañón Health Research Institute (IiSGM), 28009 Madrid, SpainGregorio Marañón Health Research Institute (IiSGM), 28009 Madrid, SpainGregorio Marañón Health Research Institute (IiSGM), 28009 Madrid, SpainGregorio Marañón Health Research Institute (IiSGM), 28009 Madrid, SpainGenomics Unit, Gregorio Marañón General University Hospital, Gregorio Marañón Health Research Institute (IiSGM), 28009 Madrid, SpainGregorio Marañón Health Research Institute (IiSGM), 28009 Madrid, SpainThe familial occurrence of hematological malignancies has been underappreciated. Recent studies suggest that up to 15% of adults with myeloid neoplasms carry germline pathogenic variants in cancer-predisposing genes. This study aimed to identify the underlying germline predisposition variant in patients with a strong family or personal onco-hematological history using whole exome sequencing on sixteen uncharacterized individuals. It was carried out in two groups of patients, one with samples available from two affected relatives (Cohort A) and one with available samples from the index case (Cohort B). In Cohort A, six families were characterized. Two families shared variants in genes associated with DNA damage response and involved in cancer development (<i>CHEK2</i> and <i>RAD54L</i>). Pathogenic or likely pathogenic germline variants were also found in novel candidate genes (<i>NFATC2</i> and <i>TC2N</i>). In two families, any relevant pathogenic or likely pathogenic genomic variants were identified. In Cohort B, four additional index cases were analyzed. Three of them harbor clinically relevant variants in genes with a probable role in the development of inherited forms of hematological malignancies (<i>GATA1</i>, <i>MSH4</i> and <i>PRF1</i>). Overall, whole exome sequencing is a useful approach to achieve a further characterization of these patients and their mutational spectra. Moreover, further investigations may help improve optimization for disease management of affected patients and their families.https://www.mdpi.com/2072-6694/15/3/944predisposition syndromeswhole-exome sequencingcancer susceptibilityhematological malignanciesgermline mutation |
| spellingShingle | Cristina Andrés-Zayas Julia Suárez-González María Chicano-Lavilla Mariana Bastos Oreiro Gabriela Rodríguez-Macías Patricia Font López Santiago Osorio Prendes Gillen Oarbeascoa Royuela Patricia García Ramírez Rocío Nieves Salgado Ignacio Gómez-Centurión Diego Carbonell Muñoz Paula Muñiz Mi Kwon José Luis Díez-Martín Ismael Buño Carolina Martínez-Laperche Novel Candidate <i>loci</i> and Pathogenic Germline Variants Involved in Familial Hematological Malignancies Revealed by Whole-Exome Sequencing Cancers predisposition syndromes whole-exome sequencing cancer susceptibility hematological malignancies germline mutation |
| title | Novel Candidate <i>loci</i> and Pathogenic Germline Variants Involved in Familial Hematological Malignancies Revealed by Whole-Exome Sequencing |
| title_full | Novel Candidate <i>loci</i> and Pathogenic Germline Variants Involved in Familial Hematological Malignancies Revealed by Whole-Exome Sequencing |
| title_fullStr | Novel Candidate <i>loci</i> and Pathogenic Germline Variants Involved in Familial Hematological Malignancies Revealed by Whole-Exome Sequencing |
| title_full_unstemmed | Novel Candidate <i>loci</i> and Pathogenic Germline Variants Involved in Familial Hematological Malignancies Revealed by Whole-Exome Sequencing |
| title_short | Novel Candidate <i>loci</i> and Pathogenic Germline Variants Involved in Familial Hematological Malignancies Revealed by Whole-Exome Sequencing |
| title_sort | novel candidate i loci i and pathogenic germline variants involved in familial hematological malignancies revealed by whole exome sequencing |
| topic | predisposition syndromes whole-exome sequencing cancer susceptibility hematological malignancies germline mutation |
| url | https://www.mdpi.com/2072-6694/15/3/944 |
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