Distinctive localization and MRI features correlate of molecular subgroups in adult medulloblastoma

Zhao, Fu; Li, Chunde; Zhou, Qiangyi; Qu, Peiran; Wang, Bo; Wang, Xin; Zhang, Shun; Wang, Xingchao; Zhao, Chi; Zhang, Jing; Luo, Lin; Lin, Aiming; Xu, Lei

doi:10.1007/s11060-017-2581-y

Cited by 23 publications

(40 citation statements)

References 27 publications

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“…However, Lastowska et al [24] reported weak or minimal enhancement in 3 of 6 (50%) WNT-subgroup medulloblastoma. In their cohort of adult WNT-pathway medulloblastoma, Zhao et al [28] found significant contrast enhancement in all 17 patients, which was either heterogeneous (82%) or solid (18%). In their cohort of 17 patients with WNT-pathway medulloblastoma, Dasgupta et al [31] reported intense contrast enhancement in all patients; 53% showed homogeneous enhancement, while the enhancement pattern was inhomogeneous in the remaining 47% of patients.…”

Section: Contrast-enhancement Patternmentioning

confidence: 97%

“…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][22][23][24][25][26][27][28][29][30][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.…”

Section: Specific Imaging Features In Medulloblastoma Subgroupsmentioning

confidence: 99%

“…The anatomic location of WNT-subgroup tumors was found to be similar even in adult WNT-subgroup tumors (n = 4), with 75% being or reaching the midline in the IVth ventricle [27] . In an exclusive cohort of adult medulloblastomas, Zhao et al [28] 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 nucleus or both.…”

Section: Anatomic Locationmentioning

confidence: 99%

“…Absence of hydrocephalus, macrometastases, and hemorrohage was suggestive of WNT-MB SHH-MB was associated with larger tumor volume and edema Contact with lower rhombic lip and hemorrhage were relatively common in group 4 tumors Zhao et al . [28] , 2017 Adult MB…”

Section: Conventional Mri Featuresmentioning

confidence: 99%

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Radiogenomics of medulloblastoma: imaging surrogates of molecular biology

Dasgupta¹,

Gupta²

2018

JTGG

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Medulloblastoma is a heterogeneous disease comprising four molecular subgroups-wingless (WNT), sonic hedge hog (SHH), group 3, and group 4, with distinct developmental origins, unique transcriptional profiles, diverse phenotypes, and varying clinical outcomes. Magnetic resonance imaging (MRI) is the preferred first-line imaging modality in the diagnosis and staging of suspected brain tumors including medulloblastoma. It is being increasingly recognized that imaging features reflect underlying disease biology that can serve as independent predictive and prognostic biomarkers. Radiogenomics is an emerging field of research that aims to define relationships between non-invasive imaging features (radio-phenotypes) and genomic data/molecular markers (molecular phenotypes). Recent studies have reported encouraging data regarding imaging genomics of medulloblastoma with certain MRI features correlating with specific molecular subgroups. These include lateralized cerebellar location for SHH-subgroup; cerebellopontine angle location for WNT-subgroup; and inferior location with dilation of superior recess of the IVth ventricle for group 4 tumors. Minimal enhancement of primary tumor and ependymal metastases (infundibular/suprasellar) with mismatching pattern is a specific feature of group 4 medulloblastoma. A 5-metabolite signature profile on magnetic resonance spectroscopy reliably differentiates SHH-subgroup from non-WNT/non-SHH medulloblastoma. SHH-specific binary nomogram (location on horizontal and vertical axis, relationship with dorsal brainstem, pattern of contrast-enhancement, and peri-tumoral edema as discriminating imaging features) is associated with excellent predictive accuracy, followed by group 4-specific nomogram, with suboptimal accuracy of WNT and group 3-specific nomograms. The advent of deep machine-learning techniques and convoluted artificial neural networks should provide unique opportunities to further improve the accuracy of such radiogenomic correlation and prediction.

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Section: Contrast-enhancement Patternmentioning

confidence: 97%

Section: Specific Imaging Features In Medulloblastoma Subgroupsmentioning

confidence: 99%

Section: Anatomic Locationmentioning

confidence: 99%

Section: Conventional Mri Featuresmentioning

confidence: 99%

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Radiogenomics of medulloblastoma: imaging surrogates of molecular biology

Dasgupta¹,

Gupta²

2018

JTGG

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“…SHH-MBs are more often located in the lateral cerebellum (hemispheres, H) whereas the other MB subgroups are mainly found in the midline (vermis, V) (15,16). Notably, adult SHH-MBs in particular preferentially arise in the H compared with infant SHH-MBs (17). One limited study in two mouse models also indicated preferential occurrence of SHH-MB in the H (18).…”

mentioning

confidence: 99%

Lateral cerebellum is preferentially sensitive to high sonic hedgehog signaling and medulloblastoma formation

Tan

Wojcinski

Rallapalli

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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The main cell of origin of the Sonic hedgehog (SHH) subgroup of medulloblastoma (MB) is granule cell precursors (GCPs), a SHH-dependent transient amplifying population in the developing cerebellum. SHH-MBs can be further subdivided based on molecular and clinical parameters, as well as location because SHH-MBs occur preferentially in the lateral cerebellum (hemispheres). Our analysis of adult patient data suggests that tumors with Smoothened () mutations form more specifically in the hemispheres than those with Patched 1 () mutations. Using sporadic mouse models of SHH-MB with the two mutations commonly seen in adult MB, constitutive activation of () or loss-of-, we found that regardless of timing of induction or type of mutation, tumors developed primarily in the hemispheres, with -mutants indeed showing a stronger specificity. We further uncovered that GCPs in the hemispheres are more susceptible to high-level SHH signaling compared with GCPs in the medial cerebellum (vermis), as more or -mutant hemisphere cells remain undifferentiated and show increased tumorigenicity when transplanted. Finally, we identified location-specific GCP gene-expression profiles, and found that deletion of the genes most highly expressed in the hemispheres () or vermis (Engrailed1) showed opposing effects on GCP differentiation. Our studies thus provide insights into intrinsic differences within GCPs that impact on SHH-MB progression.

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