A very rare cancer in Down syndrome: medulloblastoma. Epidemiological data from 13 countries

Abstract

Persons with Down syndrome (DS) uniquely have an increased frequency of leukemias but a decreased total frequency of solid tumors. The distribution and frequency of specific types of brain tumors have never been studied in DS. We evaluated the frequency of primary neural cell embryonal tumors and gliomas in a large international data set. The observed number of children with DS having a medulloblastoma, central nervous system primitive neuroectodermal tumor (CNS-PNET) or glial tumor was compared to the expected number. Data were collected from cancer registries or brain tumor registries in 13 countries of Europe, America, Asia and Oceania. The number of DS children with each category of tumor was treated as a Poisson variable with mean equal to 0.000884 times the total number of registrations in that category. Among 8,043 neural cell embryonal tumors (6,882 medulloblastomas and 1,161 CNS-PNETs), only one patient with medulloblastoma had DS, while 7.11 children in total and 6.08 with medulloblastoma were expected to have DS. (p 0.016 and 0.0066 respectively). Among 13,797 children with glioma, 10 had DS, whereas 12.2 were expected. Children with DS appear to be specifically protected against primary neural cell embryonal tumors of the CNS, whereas gliomas occur at the same frequency as in the general population. A similar protection against neuroblastoma, the principal extracranial neural cell embryonal tumor, has been observed in children with DS. Additional genetic material on the supernumerary chromosome 21 may protect against embryonal neural cell tumor development.

Chronic up-regulation of the SHH pathway normalizes some developmental effects of trisomy in Ts65Dn mice

“…Reduced MB incidence has been reported in people with DS (Satge et al, 2013), however, we did not see a reduced incidence of MB in our Ts; Ptch1 +/− mice, despite that fact that Ts65Dn mice are protected against some cancers (Sussan et al, 2008; Yang and Reeves, 2011). The Ptch1 +/− mice develop a specific subtype of MB that frequently occurs with mutations in the SHH pathway in people (Matsuo et al, 2013).…”

“…A single report indicates that MB is rare among people with DS (Satge et al, 2013). We found no impact of trisomy on overall frequency of MB in the Ptch1 +/− mice that took part in our behavioral study (euploid = 29%; trisomic = 30%; age 10–24 weeks).…”

Trisomy 21 Represses Cilia Formation and Function

“…Since cancer cells often exhibit chromosome duplications, aneuploidy may impact tumorigenesis through dosage-dependent effects on cilia. In support of this possibility, individuals with DS are resistant to many solid tumors, including Shh-dependent medulloblastomas (Satgé et al., 2013). Thus, an extra copy of the PCNT gene may contribute to both developmental pathologies and beneficial tumor resistance in DS individuals.…”

Low risk of solid tumors in persons with Down syndrome

“…A case of retinoblastoma was the only nonhematologic tumor identified among children younger than 15 years of age in this study, confirming the paucity of embryonic tumors such as neuroblastoma, Wilms tumor, 11 and medulloblastoma. 12 The risk of leukemia is very high among children with Down syndrome younger than 5 years of age, with an SIR of 27 for ALL and 114 for acute myeloid leukemia. The risk for leukemia, especially ALL, remains elevated until 30 years of age.…”