Lymphoma Predisposing Gene in an Extended Family: CD70 Signaling Defect
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ORIGINAL ARTICLE
Lymphoma Predisposing Gene in an Extended Family: CD70 Signaling Defect Khusan Khodzhaev 1,2 & Sema Buyukkapu Bay 3 & Rejin Kebudi 3 & Didem Altindirek 1,2 & Aysenur Kaya 4 & Yucel Erbilgin 1 & Ozden Hatirnaz Ng 5 & Ayca Kiykim 6 & Funda Cipe Erol 4 & Feride Sen Zengin 7 & Sinem Firtina 8 & Yuk Yin Ng 9 & Basak Adakli Aksoy 10 & Muge Sayitoglu 1 Received: 18 February 2020 / Accepted: 26 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Genome-wide sequencing studies in pediatric cancer cohorts indicate that about 10% of patients have germline mutations within cancer predisposition genes. Within this group, primary immune deficiencies take the priority regarding the vulnerability of the patients to infectious agents and the difficulties of cancer management. On the other hand, early recognition of these diseases may offer specific targeted therapies and hematopoietic stem cell transplantation as an option. Besides therapeutic benefits, early diagnosis will provide genetic counseling for the family members. Within this context, an extended family with multiple consanguineous marriages and affected individuals, who presented with combined immune deficiency (CID) and/or Hodgkin lymphoma phenotype, were examined by exome sequencing. A pathogenic homozygous missense CD70 variation was detected (NM_001252.5:c332C>T) in concordance with CD70 phenotype and familial segregation was confirmed. CD70 variations in patients with CID and malignancy have very rarely been reported. This paper reports extended family with multiple affected members with CID and malignancy carrying a missense CD70 variation, and reviews the rare cases reported in the literature. Primary immune deficiencies appear to be a potential cause for pediatric cancers. Better focusing on these inborn disorders to prevent or make an early diagnosis of malignant transformation and reduce mortalities is important. Keywords CD70 . immune deficiency . lymphoma . EBV . malignancies
Introduction The last decade has seen an enormous increase in research on genetic susceptibility to childhood cancer, which has led to
many important insights. Germline components of cancer predisposition showed that up to 10% of children and adolescents with cancer are associated with inherited mutations. Identification of germline alterations is very important for
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10875-020-00816-4) contains supplementary material, which is available to authorized users. * Rejin Kebudi [email protected] 1
Aziz Sancar Institute of Experimental Medicine, Genetics Department, Istanbul University, Istanbul Turkey
2
Institute of Health Sciences, Istanbul University, Istanbul Turkey
3
Oncology Institute, Division of Pediatric Hematology-Oncology, Istanbul University, Istanbul Turkey
4
Faculty of Medicine, Department of Pediatric Allergy Immunology, Istinye University, Istanbul Turkey
5
Department of Medical Biology, Acıbadem Mehmet Ali Aydınlar
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