| Title |
SHH desmoplastic/nodular medulloblastoma and Gorlin syndrome in the setting of Down syndrome: case report, molecular profiling, and review of the literature
|
|---|---|
| Published in |
Child's Nervous System, July 2016
|
| DOI | 10.1007/s00381-016-3185-0 |
| Pubmed ID | |
| Authors |
Ross Mangum, Elizabeth Varga, Daniel R. Boué, David Capper, Martin Benesch, Jeffrey Leonard, Diana S. Osorio, Christopher R. Pierson, Nicholas Zumberge, Felix Sahm, Daniel Schrimpf, Stefan M. Pfister, Jonathan L. Finlay |
| Abstract |
Individuals with Down syndrome (DS) have an increased risk of acute leukemia compared to a markedly decreased incidence of solid tumors. Medulloblastoma, the most common malignant brain tumor of childhood, is particularly rare in the DS population, with only one published case. As demonstrated in a mouse model, DS is associated with cerebellar hypoplasia and a decreased number of cerebellar granule neuron progenitor cells (CGNPs) in the external granule cell layer (EGL). Treatment of these mice with sonic hedgehog signaling pathway (Shh) agonists promote normalization of CGNPs and improved cognitive functioning. We describe a 21-month-old male with DS and concurrent desmoplastic/nodular medulloblastoma (DNMB)-a tumor derived from Shh dysregulation and over-activation of CGNPs. Molecular profiling further classified the tumor into the new consensus SHH molecular subgroup. Additional testing revealed a de novo heterozygous germ line mutation in the PTCH1 gene encoding a tumor suppressor protein in the Shh pathway. The developmental failure of CGNPs in DS patients offers a plausible explanation for the rarity of medulloblastoma in this population. Conversely, patients with PTCH1 germline mutations experience Shh overstimulation resulting in Gorlin (Nevoid Basal Cell Carcinoma) syndrome and an increased incidence of malignant transformation of CGNPs leading to medulloblastoma formation. This represents the first documented report of an individual with DS simultaneously carrying PTCH1 germline mutation. We have observed a highly unusual circumstance in which the PTCH1 mutation appears to "trump" the effects of DS in causation of Shh-activated medulloblastoma. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 27 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Other | 3 | 11% |
| Student > Doctoral Student | 3 | 11% |
| Student > Bachelor | 3 | 11% |
| Student > Ph. D. Student | 3 | 11% |
| Student > Postgraduate | 3 | 11% |
| Other | 2 | 7% |
| Unknown | 10 | 37% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 15 | 56% |
| Nursing and Health Professions | 1 | 4% |
| Social Sciences | 1 | 4% |
| Psychology | 1 | 4% |
| Unknown | 9 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 July 2016.
All research outputs
#20,336,031
of 22,881,154 outputs
Outputs from Child's Nervous System
#1,796
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Outputs of similar age
#318,478
of 364,404 outputs
Outputs of similar age from Child's Nervous System
#48
of 79 outputs
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