Constitutional mismatch repair deficiency-associated brain tumors: report from the European C4CMMRD consortium.
MMR biallelic germline mutation
brain tumor
café-au-lait spot
childhood cancer
constitutional mismatch repair deficiency
high-grade glioma
predisposition
Journal
Neuro-oncology advances
ISSN: 2632-2498
Titre abrégé: Neurooncol Adv
Pays: England
ID NLM: 101755003
Informations de publication
Date de publication:
Historique:
entrez:
10
7
2020
pubmed:
10
7
2020
medline:
10
7
2020
Statut:
epublish
Résumé
Malignant brain tumors (BT) are among the cancers most frequently associated with constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer predisposition syndrome resulting from biallelic germline mutations in mismatch repair genes. This study analyzed data from the European "Care for CMMRD" (C4CMMRD) database to describe their clinical characteristics, treatments, and outcome with the aim of improving its diagnosis/treatment. Retrospective analysis of data on patients with CMMRD and malignant BT from the C4CMMRD database up to July 2017. Among the 87 registered patients, 49 developed 56 malignant BTs: 50 high-grade gliomas (HGG) (with giant multinucleated cells in 16/21 histologically reviewed tumors) and 6 embryonal tumors. The median age at first BT was 9.2 years [1.1-40.6], with nine patients older than 18. Twenty-seven patients developed multiple malignancies (including16 before the BT). Most patients received standard treatment, and eight patients immunotherapy for relapsed HGG. The 3- and 5-year overall survival (OS) rates were 30% (95% CI: 19-45) and 22% (95% CI: 12-37) after the first BT, with worse prognosis for HGG (3-year OS = 20.5%). Six patients were alive (median follow-up 2.5 years) and 43 dead (38 deaths, 88%, were BT-related). Other CMMRD-specific features were café-au-lait macules (40/41), multiple BTs (5/15), developmental brain anomalies (11/15), and consanguinity (20/38 families). Several characteristics could help suspecting CMMRD in pediatric malignant BTs: giant cells on histology, previous malignancies, parental consanguinity, café-au-lait macules, multiple BTs, and developmental brain anomalies. The prognosis of CMMRD-associated BT treated with standard therapies is poor requiring new therapeutic up-front approaches.
Sections du résumé
BACKGROUND
BACKGROUND
Malignant brain tumors (BT) are among the cancers most frequently associated with constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer predisposition syndrome resulting from biallelic germline mutations in mismatch repair genes. This study analyzed data from the European "Care for CMMRD" (C4CMMRD) database to describe their clinical characteristics, treatments, and outcome with the aim of improving its diagnosis/treatment.
METHODS
METHODS
Retrospective analysis of data on patients with CMMRD and malignant BT from the C4CMMRD database up to July 2017.
RESULTS
RESULTS
Among the 87 registered patients, 49 developed 56 malignant BTs: 50 high-grade gliomas (HGG) (with giant multinucleated cells in 16/21 histologically reviewed tumors) and 6 embryonal tumors. The median age at first BT was 9.2 years [1.1-40.6], with nine patients older than 18. Twenty-seven patients developed multiple malignancies (including16 before the BT). Most patients received standard treatment, and eight patients immunotherapy for relapsed HGG. The 3- and 5-year overall survival (OS) rates were 30% (95% CI: 19-45) and 22% (95% CI: 12-37) after the first BT, with worse prognosis for HGG (3-year OS = 20.5%). Six patients were alive (median follow-up 2.5 years) and 43 dead (38 deaths, 88%, were BT-related). Other CMMRD-specific features were café-au-lait macules (40/41), multiple BTs (5/15), developmental brain anomalies (11/15), and consanguinity (20/38 families).
CONCLUSIONS
CONCLUSIONS
Several characteristics could help suspecting CMMRD in pediatric malignant BTs: giant cells on histology, previous malignancies, parental consanguinity, café-au-lait macules, multiple BTs, and developmental brain anomalies. The prognosis of CMMRD-associated BT treated with standard therapies is poor requiring new therapeutic up-front approaches.
Identifiants
pubmed: 32642664
doi: 10.1093/noajnl/vdz033
pii: vdz033
pmc: PMC7212899
doi:
Types de publication
Journal Article
Langues
eng
Pagination
vdz033Informations de copyright
© The Author(s) 2019. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
Références
Neurosurgery. 2015 Jul;77(1):E145-52; discussion E152
pubmed: 25850602
Oncotarget. 2018 Oct 23;9(83):35458-35469
pubmed: 30459937
Int J Oncol. 2004 Apr;24(4):1039-47
pubmed: 15010846
J Natl Cancer Inst. 2015 Jun 24;107(9):
pubmed: 26109217
Eur J Hum Genet. 2018 Mar;26(3):440-444
pubmed: 29302048
Pediatr Blood Cancer. 2016 Mar;63(3):418-27
pubmed: 26544533
J Clin Oncol. 2019 Feb 20;37(6):461-470
pubmed: 30608896
AJNR Am J Neuroradiol. 2018 Oct;39(10):1943-1946
pubmed: 30166433
Gastroenterology. 2015 Oct;149(4):1017-29.e3
pubmed: 26116798
Cancer Res. 1999 Jan 15;59(2):290-3
pubmed: 9927033
J Med Genet. 2014 Jun;51(6):355-65
pubmed: 24737826
AJNR Am J Neuroradiol. 2019 Jun;40(6):E30-E31
pubmed: 31072978
Nat Genet. 2015 Mar;47(3):257-62
pubmed: 25642631
J Clin Oncol. 2016 Jul 1;34(19):2206-11
pubmed: 27001570
N Engl J Med. 2015 Jun 25;372(26):2509-20
pubmed: 26028255
Eur J Cancer. 2017 Oct;84:290-303
pubmed: 28846956
Annu Rev Biochem. 2005;74:681-710
pubmed: 15952900
Cancer Res. 1995 Sep 1;55(17):3721-5
pubmed: 7641183
PLoS One. 2014 Mar 17;9(3):e91319
pubmed: 24637877
J Med Genet. 2019 Feb;56(2):53-62
pubmed: 30415209
Carcinogenesis. 2001 Dec;22(12):1931-7
pubmed: 11751422
Neuropathol Appl Neurobiol. 2018 Feb;44(2):233-239
pubmed: 29130549
Hum Mutat. 2019 May;40(5):649-655
pubmed: 30740824
Acta Neuropathol. 2007 Aug;114(2):97-109
pubmed: 17618441
Cancer Lett. 2017 Sep 10;403:159-164
pubmed: 28645564
DNA Repair (Amst). 2016 Feb;38:155-162
pubmed: 26746812
J Clin Oncol. 2018 Apr 1;36(10):951-958
pubmed: 29412784
Childs Nerv Syst. 2016 Mar;32(3):553-7
pubmed: 26293676
Oncologist. 2018 Dec;23(12):1401-1406
pubmed: 30104292
Pediatr Blood Cancer. 2012 Oct;59(4):652-6
pubmed: 22180144
Front Immunol. 2018 Jul 02;9:1506
pubmed: 30013564
Cancer Res. 1999 Jan 15;59(2):294-7
pubmed: 9927034
Hum Mutat. 2013 Jun;34(6):847-52
pubmed: 23483711
Cancer Cell. 2015 Jul 13;28(1):11-3
pubmed: 26175412
Cancer Res. 2015 Aug 1;75(15):3127-38
pubmed: 26025730
Clin Cancer Res. 2017 Jun 1;23(11):e32-e37
pubmed: 28572265
Clin Genet. 2017 Apr;91(4):507-519
pubmed: 27779754
J Med Genet. 2014 May;51(5):283-93
pubmed: 24556086
Lancet Oncol. 2018 Jun;19(6):785-798
pubmed: 29753700
Eur J Hum Genet. 2018 Oct;26(10):1417-1423
pubmed: 29904176
Gastroenterology. 2017 May;152(6):1605-1614
pubmed: 28363489
Cancer Res. 2017 Jan 1;77(1):198-206
pubmed: 27793847
Lancet. 2011 Dec 17;378(9809):2081-7
pubmed: 22036019
Eur J Hum Genet. 2009 Jul;17(7):919-27
pubmed: 19156169
J Med Genet. 2015 Nov;52(11):770-8
pubmed: 26318770
Pediatr Blood Cancer. 2011 Dec 1;57(6):1067-70
pubmed: 21674763
Clin Genet. 2009 Jul;76(1):1-18
pubmed: 19659756
Acta Neuropathol. 2016 Jun;131(6):803-20
pubmed: 27157931
Clin Cancer Res. 2007 Apr 1;13(7):2038-45
pubmed: 17404084