CONSTITUTIONAL MISSMATCH DEFECT REPAIR DISORDER (CMMRD) IN PEDIATRIC HIGH GRADE GLIOMA

Objective: Pediatric high grade gliomas(HGG) have dismal prognosis with median survival of 9-15 months after standard radio-chemptherapy. Recent molecular investigations revealed a missmatch repair defect called Constitutional Mismatch Repair Deficiency (CMMRD), which induce pediatric HGG. In CMMRD,...

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Autores principales:	Bahattin Tanrıkulu, Ayça Erşen Danyeli, Cengiz Canpolat, M. Memet Özek
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Diseases of the blood and blood-forming organs RC633-647.5
Acceso en línea:	https://doaj.org/article/223409e80164491b9ecb932757f02299
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spelling	oai:doaj.org-article:223409e80164491b9ecb932757f022992021-11-10T04:34:05ZCONSTITUTIONAL MISSMATCH DEFECT REPAIR DISORDER (CMMRD) IN PEDIATRIC HIGH GRADE GLIOMA2531-137910.1016/j.htct.2021.10.1003https://doaj.org/article/223409e80164491b9ecb932757f022992021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2531137921011500https://doaj.org/toc/2531-1379Objective: Pediatric high grade gliomas(HGG) have dismal prognosis with median survival of 9-15 months after standard radio-chemptherapy. Recent molecular investigations revealed a missmatch repair defect called Constitutional Mismatch Repair Deficiency (CMMRD), which induce pediatric HGG. In CMMRD, there are mutations at least one of the mismatch repair(MMR) genes in both tumoral and non-tumoral DNA. Patients generally have cafe au lait spots resembling the ones in NF-1. Methodology: Forty-four pediatric high-grade glioma cases operated in our clinic between 2015-2021 were included in the study. PMS2, MLH1, MSH6, MSH2 immunohistochemical antibodies were applied to the sections prepared from paraffin blocks with tumors of these 44 cases. Next generation Sequencing (NGS) Custom Panel for Brain Tumors was performed with DNA and RNA obtained from neoplastic tissue of 2 cases and germline NGS analysis was performed with DNA obtained from peripheral blood in 1 case. Results: MMR protein expression loss was detected in 11 (25%) cases. In 5 (45%) of these 11 cases, MMR protein loss was detected in both neoplastic and non-neoplastic tissue, and these cases were considered as CMMRD. NGS performed in 2 of these 5 cases revealed a hypermutant profile. At least one MMR protein loss was found only in the neoplastic tissue in 6 (55%) of 11 cases, and PMS2 deficiency was the most common. In 1 of these 6 cases, MSH6 deficiency was shown as germline by NGS. Conclusion: CMMRD and MMRD, are disorders with close relationship with pediatric high grade gliomas. Since CMMRD cases also may have cafe au lait spots, they should not be misdiagnosed as NF 1. Temozolomide induce more aggressive tumors in CMMRD ve MMRD, therefore its use is not suggested in those cases. Preliminary literature data advocate use of immunotherapy instead. All pediatric HGG cases should be evaluated for CMMRD and MMRD with molecular investigations to understand their biology.Bahattin TanrıkuluAyça Erşen DanyeliCengiz CanpolatM. Memet ÖzekElsevierarticleDiseases of the blood and blood-forming organsRC633-647.5ENHematology, Transfusion and Cell Therapy, Vol 43, Iss , Pp S29-S30 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the blood and blood-forming organs RC633-647.5
spellingShingle	Diseases of the blood and blood-forming organs RC633-647.5 Bahattin Tanrıkulu Ayça Erşen Danyeli Cengiz Canpolat M. Memet Özek CONSTITUTIONAL MISSMATCH DEFECT REPAIR DISORDER (CMMRD) IN PEDIATRIC HIGH GRADE GLIOMA
description	Objective: Pediatric high grade gliomas(HGG) have dismal prognosis with median survival of 9-15 months after standard radio-chemptherapy. Recent molecular investigations revealed a missmatch repair defect called Constitutional Mismatch Repair Deficiency (CMMRD), which induce pediatric HGG. In CMMRD, there are mutations at least one of the mismatch repair(MMR) genes in both tumoral and non-tumoral DNA. Patients generally have cafe au lait spots resembling the ones in NF-1. Methodology: Forty-four pediatric high-grade glioma cases operated in our clinic between 2015-2021 were included in the study. PMS2, MLH1, MSH6, MSH2 immunohistochemical antibodies were applied to the sections prepared from paraffin blocks with tumors of these 44 cases. Next generation Sequencing (NGS) Custom Panel for Brain Tumors was performed with DNA and RNA obtained from neoplastic tissue of 2 cases and germline NGS analysis was performed with DNA obtained from peripheral blood in 1 case. Results: MMR protein expression loss was detected in 11 (25%) cases. In 5 (45%) of these 11 cases, MMR protein loss was detected in both neoplastic and non-neoplastic tissue, and these cases were considered as CMMRD. NGS performed in 2 of these 5 cases revealed a hypermutant profile. At least one MMR protein loss was found only in the neoplastic tissue in 6 (55%) of 11 cases, and PMS2 deficiency was the most common. In 1 of these 6 cases, MSH6 deficiency was shown as germline by NGS. Conclusion: CMMRD and MMRD, are disorders with close relationship with pediatric high grade gliomas. Since CMMRD cases also may have cafe au lait spots, they should not be misdiagnosed as NF 1. Temozolomide induce more aggressive tumors in CMMRD ve MMRD, therefore its use is not suggested in those cases. Preliminary literature data advocate use of immunotherapy instead. All pediatric HGG cases should be evaluated for CMMRD and MMRD with molecular investigations to understand their biology.
format	article
author	Bahattin Tanrıkulu Ayça Erşen Danyeli Cengiz Canpolat M. Memet Özek
author_facet	Bahattin Tanrıkulu Ayça Erşen Danyeli Cengiz Canpolat M. Memet Özek
author_sort	Bahattin Tanrıkulu
title	CONSTITUTIONAL MISSMATCH DEFECT REPAIR DISORDER (CMMRD) IN PEDIATRIC HIGH GRADE GLIOMA
title_short	CONSTITUTIONAL MISSMATCH DEFECT REPAIR DISORDER (CMMRD) IN PEDIATRIC HIGH GRADE GLIOMA
title_full	CONSTITUTIONAL MISSMATCH DEFECT REPAIR DISORDER (CMMRD) IN PEDIATRIC HIGH GRADE GLIOMA
title_fullStr	CONSTITUTIONAL MISSMATCH DEFECT REPAIR DISORDER (CMMRD) IN PEDIATRIC HIGH GRADE GLIOMA
title_full_unstemmed	CONSTITUTIONAL MISSMATCH DEFECT REPAIR DISORDER (CMMRD) IN PEDIATRIC HIGH GRADE GLIOMA
title_sort	constitutional missmatch defect repair disorder (cmmrd) in pediatric high grade glioma
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/223409e80164491b9ecb932757f02299
work_keys_str_mv	AT bahattintanrıkulu constitutionalmissmatchdefectrepairdisordercmmrdinpediatrichighgradeglioma AT aycaersendanyeli constitutionalmissmatchdefectrepairdisordercmmrdinpediatrichighgradeglioma AT cengizcanpolat constitutionalmissmatchdefectrepairdisordercmmrdinpediatrichighgradeglioma AT mmemetozek constitutionalmissmatchdefectrepairdisordercmmrdinpediatrichighgradeglioma
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CONSTITUTIONAL MISSMATCH DEFECT REPAIR DISORDER (CMMRD) IN PEDIATRIC HIGH GRADE GLIOMA

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