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| Home > Articles > Published articles > The challenge of diagnosing constitutional mismatch repair deficiency syndrome in brain malignancies from young individuals |
(Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Centro de Investigación Biomédica en Red de Cáncer) (Centro de Investigación Biomédica en Red de Cáncer) (Institut Català d'Oncologia) (Institució Catalana de Recerca i Estudis Avançats) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)| Date: | 2021 |
| Abstract: | Biallelic germline mismatch repair (MMR) gene (MLH1, MSH2, MSH6, and PMS2) mutations are an extremely rare event that causes constitutional mismatch repair deficiency (CMMRD) syndrome. CMMRD is underdiagnosed and often debuts with pediatric malignant brain tumors. A high degree of clinical awareness of the CMMRD phenotype is needed to identify new cases. Immunohistochemical (IHC) assessment of MMR protein expression and analysis of microsatellite instability (MSI) are the first tools with which to initiate the study of this syndrome in solid malignancies. MMR IHC shows a hallmark pattern with absence of staining in both neoplastic and non-neoplastic cells for the biallelic mutated gene. However, MSI often fails in brain malignancies. The aim of this report is to draw attention to the peculiar IHC profile that characterizes CMMRD syndrome and to review the difficulties in reaching an accurate diagnosis by describing the case of two siblings with biallelic MSH6 germline mutations and brain tumors. Given the difficulties involved in early diagnosis of CMMRD we propose the use of the IHC of MMR proteins in all malignant brain tumors diagnosed in individuals younger than 25 years-old to facilitate the diagnosis of CMMRD and to select those neoplasms that will benefit from immunotherapy treatment. |
| Grants: | Agencia Estatal de Investigación PID2019-111254RB-I00 Ministerio de Economía y Competitividad SAF2015-68016-R Agencia Estatal de Investigación RTI2018-094049-B-I00 Ministerio de Economía y Competitividad SAF2014-55000 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR1080 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR1282 "la Caixa" Foundation PR/GN18/51140001 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Constitutional mismatch repair deficiency syndrome ; MMR gene expression ; Immunohistochemistry ; MSH6 gene 1. Introductio |
| Published in: | International journal of molecular sciences, Vol. 22 Núm. 9 (2021) , p. 4629, ISSN 1422-0067 |
