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Dasgupta et al. J Transl Genet Genom 2018;2:15. I https://doi.org/10.20517/jtgg.2018.21 Page 3 of 15

markers [18-20] . In its simplest form, semantic imaging features like size/volume, margins/borders, density or
intensity characteristics, contrast enhancement, edema, necrosis, hemorrhage, calcification, can be assessed
and quantified visually for correlation with molecular markers either singly or in combination. Introduction
of computer-based algorithms has not only refined the assessment of semantic features, but also allows
extraction of agnostic features (histograms, textures, wavelets, and fractal dimensions), which generally
go beyond human capability. Such automated high-throughput processing significantly reduces time and
virtually eliminates inter-observer variability often associated with human interpretation. This review
dissects and discusses the current state of knowledge regarding the radiogenomics of medulloblastoma.

Specific imaging features in medulloblastoma subgroups
In the last decade or so, several investigators from across the world have tried to correlate semantic imaging
features with molecular subgrouping in medulloblastoma. All such studies [21-31] reporting on the imaging
genomics of medulloblastoma are briefly summarized in Table 1. While it is quite clear that no single
imaging feature is pathognomonic of any particular subgroup, certain imaging characteristics are much
more prevalent in one subgroup compared to others and may even be highly specific for an individual
molecular subgroup. Characteristic imaging features typically seen in each of the four individual molecular
subgroups are summarized in Table 2 and illustrated in Figures 1-4.

WNT SUBGROUP MEDULLOBLASTOMA
Reportedly the rarest subgroup (comprising approximately 10% of all medulloblastoma), the WNT-
pathway medulloblastomas have the best prognosis amongst all four subgroups with 5-year overall
survival exceeding 90% in almost all studies [3-6] . They are mostly uniform in their genetic aberrations,
histological pattern, and clinical presentation. Classic histology is seen in the vast majority of WNT-
pathway medulloblastoma (> 95%), although occasional large-cell/anaplastic (LCA) variants have also been
[5,6]
reported . They are equally distributed amongst boys and girls and commonly seen in older children and
[3,6]
teenagers, but rarely ever in infants .
Anatomic location
It is hypothesized that the WNT-pathway medulloblastomas arise from neural progenitors in the dorsal
brainstem nuclei [32,33] which explains its midline location and close proximity to the dorsal brainstem. In
one of the first clinical observations of an association between molecular subgrouping and tumor location,
[21]
Teo et al. , reported 100% of WNT-subgroup medulloblastomas (n = 5) as having a midline vermian
[22]
location. Subsequently, Perreault and colleagues reported 75% of WNT-subgroup tumors (n = 14) as being
situated along the cerebellar peduncle and even extending up to the cerebellopontine angle (CPA) cistern
[23]
in accordance with their origin from brainstem nucleus. In another study, Wefers et al. reported 75% of
WNT-subgroup medulloblastomas (n = 8) touching the cuneate nucleus located in the medulla. Interestingly,
they also found these tumors to be more frequently caudal as opposed to rostral, concordant with the mouse
[32]
model study , wherein the genes associated with WNT-pathway are more expressed in the lower rhombic
lip as compared to the upper rhombic lip. The midline location (83%) with extension into CPA (17%) was
[24]
also reported by Lastowska and colleagues in WNT-pathway medulloblastoma. In an imaging study
[26]
exclusively involving children with WNT-subgroup medulloblastoma (n = 16), Patay et al. reported the
involvement of specific sites such as foramen of Luschka (75%), IVth ventricle (69%), cisterna magna (31%)
and CPA cistern (19%). The anatomic location of WNT-subgroup tumors was found to be similar even in
[27]
adult WNT-subgroup tumors (n = 4), with 75% being or reaching the midline in the IVth ventricle . In an
[28]
exclusive cohort of adult medulloblastomas, Zhao et al. reported midline vermian location in 5 of 17 (29%)
WNT-pathway tumors and lateral extension into cerebellar hemisphere or peduncle in the remaining 12 (71%)
patients. All 17 adults WNT-pathway medulloblastomas had brainstem contact with cochlear or cuneate
[29]
nucleus or both. In a cohort of 15 WNT-subgroup medulloblastoma, Mata-Mbemba et al. , reported the
tumor to be confined in midline vermian location in 33% of children, with the remaining 67% showing
extension either unilaterally or bilaterally along the lateral recess of the IVth ventricle and beyond reaching