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@ARTICLE{Lou:144570,
author = {E. Lou and A. C. Nelson and M. Kool$^*$},
title = {{D}ifferential response of {SHH}-expressing adult
medulloblastomas to the sonic hedgehog inhibitor vismodegib:
whole-genome analysis.},
journal = {Cancer biology $\&$ therapy},
volume = {20},
number = {11},
issn = {1555-8576},
address = {Georgetown, Tex.},
publisher = {Landes Bioscience},
reportid = {DKFZ-2019-02013},
pages = {1398-1402},
year = {2019},
note = {20(11):1398-1402.},
abstract = {Medulloblastoma is an aggressive primitive neuroectodermal
tumor of the cerebellum that is more common in children than
in adults. In the past decade, advances in understanding the
molecular drivers of medulloblastoma have identified four
molecular subgroups defined by experimental gene expression
profiles: the WNT pathway, sonic hedgehog (SHH) pathway, and
subgroups 3 and 4 (non-SHH/WNT). Medulloblastoma of adults
belong primarily to the SHH category. Vismodegib, an
SHH-pathway inhibitor, FDA-approved in 2012 for treatment of
basal cell carcinoma, has been used successfully in the
setting of chemorefractory medulloblastoma, but not as a
first-line therapy. In 2016, we reported a case of an adult
patient with a sustained response of an unresectable
multifocal form of adult medulloblastoma to vismodegib.
Molecular analysis in that case revealed mutations in TP53
and a cytogenetic abnormality, i17q, that is prevalent and
most often associated with subgroup 4 rather than the
SHH-activated form of medulloblastoma. Here, we report
further whole-genome analysis of that patient (designated
Patient A) as well as an additional adult patient (Patient
B) whose tumor harbored the SHH molecular subgroup but which
was unresponsive to visgmodegib therapy. Comparison of these
disparate responses highlights the challenges to tailoring
SHH-targeted treatment in individual patients with adult
medulloblastoma.},
cin = {B062 / L101},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)L101-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31423907},
doi = {10.1080/15384047.2019.1647057},
url = {https://inrepo02.dkfz.de/record/144570},
}