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

INTRODUCTION
Medulloblastoma, the most common pediatric malignant neoplasm of the central nervous system (CNS)
[1,2]
comprising 20%-25% of all childhood brain tumors belongs to the primitive embryonal group of tumors
that arises in the posterior fossa and is classified histologically as World Health Organization (WHO)
grade IV tumor. Over the last decade or so, novel biological insights into its heterogeneity have led to the
identification of various molecular subgroups with distinct developmental origins, unique transcriptional
[6]
[3-6]
profiles, diverse phenotypes, and variable clinical outcomes . The consensus classification comprising
four distinct molecular subgroups - wingless (WNT), sonic hedge hog (SHH), Group 3, and Group 4
medulloblastoma has now been incorporated in the 2016 update of the WHO classification of CNS
[7]
tumors . With rapid evolution of genomic technology, several platforms/methodologies are now available
for molecular subgrouping of medulloblastoma. These include expression profiling of a select set of marker
[8]
genes at RNA level using nanoString or real time reverse transcriptase polymerase chain reaction [9,10] ;
[11]
differential expression of select set of protein-coding genes and microRNAs ; expression of selected marker
proteins [12,13] on immunohistochemistry (IHC); and DNA methylation array [14,15] . Each of the methodologies
have their unique advantages and disadvantages with its selection left to the judgement and discretion of the
treating physician based on available resources (infrastructure and expertise), cost, and turn-around time.

Conventional imaging features of medulloblastoma
In patients with suspected brain tumors, a computed tomography (CT) scan and/or magnetic resonance
imaging (MRI) of the brain is required to arrive at a presumptive diagnosis and guide further decision-
making. Given the high propensity of neuraxial spread in medulloblastoma via cerebrospinal fluid pathways,
pre-operative imaging of the spine is also recommended in the initial diagnostic work-up of children with
posterior fossa tumors [16,17] . The features of medulloblastoma on conventional neuro-imaging have been very
well characterized and described in the indexed medical literature [16,17] . Medulloblastoma is generally seen as
a well-defined, solid, hyper-dense lesion on plain CT that shows variable enhancement post-contrast, it arises
typically from the vermis in the midline posterior fossa and fills the fourth ventricle causing obstructive
hydrocephalus; less commonly it is located laterally in the cerebellar hemisphere with or without extension
to the foramen. MRI with its exquisite anatomic resolution, multi-parametric nature, and ability to image
the entire neuraxis in one session is the preferred imaging modality for suspected medulloblastoma. On T1-
weighted images, medulloblastoma generally appears iso- to hypo-intense compared to surrounding white
matter. It exhibits variable signal intensity on T2-weighted images with densely cellular component of the
tumor being hypo-intense and lesser cellular areas being iso-intense compared to surrounding white matter.
Intra-tumoral or peri-tumoral cysts, if any, appear hyper-intense while calcification generally exhibits low
signal on T2-weighted sequences. Following intravenous gadolinium, medulloblastoma shows significant
but variable and heterogeneous contrast enhancement. Due to densely packed cells, medulloblastoma causes
restriction of diffusion with correspondingly low apparent diffusion co-efficient values.

Radiogenomics or imaging genomics
Traditionally, imaging has been used for diagnosis (characterization of lesion) and staging (assessment
of disease extent) in oncology. With regards to brain tumors, the neuro-radiology community has
predominantly focussed on correlating imaging features with histomorphology and grading. However,
as is now widely believed, images are more than just pictures [18,19] that reflect underlying disease biology
including the dynamics of complex biological processes such as gene expression, proliferation, metabolism,
[20]
and angiogenesis. Radiogenomics or imaging genomics is an exciting and emerging field of research that
aims to define relationships between non-invasive imaging features (radio-phenotypes) and genomic data/
molecular markers (molecular phenotypes). In the past few years, it has become increasingly possible to
extract meaningful information from routine images that can be utilized beyond the diagnostic and staging
roles of radiology. Radiogenomics is a multi-step process comprising sequential stages of image acquisition,
image segmentation, feature selection, feature extraction, qualification and final correlation with molecular