BACKGROUND: Medulloblastoma (MB) comprises of four molecular subtypes, Sonic hedgehog (SHH), Wingless (WNT), Groups 3 and 4. WNT-subtype MBs were found to arise from midline of the brainstem occupying the fourth ventricle while SHH-subtype occupied the cerebellar hemisphere in a small subset of patients. PROCEDURE: We tested this hypothesis in a large cohort of pediatric MBs comprising of all four molecular subtypes. RESULTS: We validated in the first comprehensive analysis of tumor location of 60 human MBs representative of the four molecular subtypes, that hemispheric tumors are significantly associated with SHH-subtype MBs while midline tumors with WNT-subtype, Group 3 and 4 MBs (P < 0.001). Nearly half of SHH-subtype MBs were midline. CONCLUSIONS: Tumor location should not be generalized to MB subtypes. SHH-subtype MBs are not exclusively hemispheric and hemispheric MBs are not always SHH-activated. It is imperative to identify subtypes in conjunction with tumor location when exploring currently available targeted therapy.
BACKGROUND:Medulloblastoma (MB) comprises of four molecular subtypes, Sonic hedgehog (SHH), Wingless (WNT), Groups 3 and 4. WNT-subtype MBs were found to arise from midline of the brainstem occupying the fourth ventricle while SHH-subtype occupied the cerebellar hemisphere in a small subset of patients. PROCEDURE: We tested this hypothesis in a large cohort of pediatric MBs comprising of all four molecular subtypes. RESULTS: We validated in the first comprehensive analysis of tumor location of 60 human MBs representative of the four molecular subtypes, that hemispheric tumors are significantly associated with SHH-subtype MBs while midline tumors with WNT-subtype, Group 3 and 4 MBs (P < 0.001). Nearly half of SHH-subtype MBs were midline. CONCLUSIONS:Tumor location should not be generalized to MB subtypes. SHH-subtype MBs are not exclusively hemispheric and hemispheric MBs are not always SHH-activated. It is imperative to identify subtypes in conjunction with tumor location when exploring currently available targeted therapy.
Authors: A Stock; M Mynarek; T Pietsch; S M Pfister; S C Clifford; T Goschzik; D Sturm; E C Schwalbe; D Hicks; S Rutkowski; B Bison; M Pham; M Warmuth-Metz Journal: AJNR Am J Neuroradiol Date: 2019-10-24 Impact factor: 3.825
Authors: M Iv; M Zhou; K Shpanskaya; S Perreault; Z Wang; E Tranvinh; B Lanzman; S Vajapeyam; N A Vitanza; P G Fisher; Y J Cho; S Laughlin; V Ramaswamy; M D Taylor; S H Cheshier; G A Grant; T Young Poussaint; O Gevaert; K W Yeom Journal: AJNR Am J Neuroradiol Date: 2018-12-06 Impact factor: 3.825
Authors: V C Keil; M Warmuth-Metz; C Reh; S J Enkirch; C Reinert; D Beier; D T W Jones; T Pietsch; H H Schild; E Hattingen; P Hau Journal: AJNR Am J Neuroradiol Date: 2017-08-10 Impact factor: 3.825
Authors: Cassie N Kline; Roger J Packer; Eugene I Hwang; David R Raleigh; Steve Braunstein; Corey Raffel; Pratiti Bandopadhayay; David A Solomon; Mariam Aboian; Soonmee Cha; Sabine Mueller Journal: Neurooncol Pract Date: 2017-08-11
Authors: S Perreault; V Ramaswamy; A S Achrol; K Chao; T T Liu; D Shih; M Remke; S Schubert; E Bouffet; P G Fisher; S Partap; H Vogel; M D Taylor; Y J Cho; K W Yeom Journal: AJNR Am J Neuroradiol Date: 2014-05-15 Impact factor: 3.825