Molecular subgroups of adult medulloblastoma: a long-term single-institution study.
Recent transcriptomic approaches have demonstrated that there are at least 4 distinct subgroups in medulloblastoma (MB); however, survival studies of molecular subgroups in adult MB have been inconclusive because of small sample sizes. The aim of this study is to investigate the molecular subgroups in adult MB and identify their clinical and prognostic implications in a large, single-institution cohort.



We determined gene expression profiles for 13 primary adult MBs. Bioinformatics tools were used to establish distinct molecular subgroups based on the most informative genes in the dataset. Immunohistochemistry with subgroup-specific antibodies was then used for validation within an independent cohort of 201 formalin-fixed MB tumors, in conjunction with a systematic analysis of clinical and histological characteristics.



Three distinct molecular variants of adult MB were identified: the SHH, WNT, and group 4 subgroups. Validation of these subgroups in the 201-tumor cohort by immunohistochemistry identified significant differences in subgroup-specific demographics, histology, and metastatic status. The SHH subgroup accounted for the majority of the tumors (62%), followed by the group 4 subgroup (28%) and the WNT subgroup (10%). Group 4 tumors had significantly worse progression-free and overall survival compared with tumors of the other molecular subtypes.



We have identified 3 subgroups of adult MB, characterized by distinct expression profiles, clinical features, pathological features, and prognosis. Clinical variables incorporated with molecular subgroup are more significantly informative for predicting adult patient outcome.
Neural Reconstructional Department, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (F.Z., J.Z., P.L.); Department of Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (L.L.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (F.Z., C.L., P.L., Z.Y., B.W., X.W., Z.W., P.L.); Department of Imaging and Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (L.A.); Section of Molecular Pathology, International Agency for Research on Cancer, World Health Organization, Lyon, France (H.O.); Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (L.X.); Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy (F.G.).
Fu
F
Zhao
Neural Reconstructional Department, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (F.Z., J.Z., P.L.); Department of Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (L.L.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (F.Z., C.L., P.L., Z.Y., B.W., X.W., Z.W., P.L.); Department of Imaging and Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (L.A.); Section of Molecular Pathology, International Agency for Research on Cancer, World Health Organization, Lyon, France (H.O.); Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (L.X.); Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy (F.G.).
Hiroko
H
Ohgaki
Neural Reconstructional Department, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (F.Z., J.Z., P.L.); Department of Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (L.L.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (F.Z., C.L., P.L., Z.Y., B.W., X.W., Z.W., P.L.); Department of Imaging and Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (L.A.); Section of Molecular Pathology, International Agency for Research on Cancer, World Health Organization, Lyon, France (H.O.); Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (L.X.); Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy (F.G.).
Lei
L
Xu
Neural Reconstructional Department, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (F.Z., J.Z., P.L.); Department of Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (L.L.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (F.Z., C.L., P.L., Z.Y., B.W., X.W., Z.W., P.L.); Department of Imaging and Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (L.A.); Section of Molecular Pathology, International Agency for Research on Cancer, World Health Organization, Lyon, France (H.O.); Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (L.X.); Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy (F.G.).
Felice
F
Giangaspero
Neural Reconstructional Department, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (F.Z., J.Z., P.L.); Department of Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (L.L.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (F.Z., C.L., P.L., Z.Y., B.W., X.W., Z.W., P.L.); Department of Imaging and Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (L.A.); Section of Molecular Pathology, International Agency for Research on Cancer, World Health Organization, Lyon, France (H.O.); Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (L.X.); Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy (F.G.).
Chunde
C
Li
Neural Reconstructional Department, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (F.Z., J.Z., P.L.); Department of Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (L.L.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (F.Z., C.L., P.L., Z.Y., B.W., X.W., Z.W., P.L.); Department of Imaging and Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (L.A.); Section of Molecular Pathology, International Agency for Research on Cancer, World Health Organization, Lyon, France (H.O.); Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (L.X.); Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy (F.G.).
Peng
P
Li
Neural Reconstructional Department, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (F.Z., J.Z., P.L.); Department of Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (L.L.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (F.Z., C.L., P.L., Z.Y., B.W., X.W., Z.W., P.L.); Department of Imaging and Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (L.A.); Section of Molecular Pathology, International Agency for Research on Cancer, World Health Organization, Lyon, France (H.O.); Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (L.X.); Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy (F.G.).
Zhijun
Z
Yang
Neural Reconstructional Department, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (F.Z., J.Z., P.L.); Department of Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (L.L.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (F.Z., C.L., P.L., Z.Y., B.W., X.W., Z.W., P.L.); Department of Imaging and Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (L.A.); Section of Molecular Pathology, International Agency for Research on Cancer, World Health Organization, Lyon, France (H.O.); Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (L.X.); Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy (F.G.).
Bo
B
Wang
Neural Reconstructional Department, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (F.Z., J.Z., P.L.); Department of Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (L.L.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (F.Z., C.L., P.L., Z.Y., B.W., X.W., Z.W., P.L.); Department of Imaging and Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (L.A.); Section of Molecular Pathology, International Agency for Research on Cancer, World Health Organization, Lyon, France (H.O.); Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (L.X.); Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy (F.G.).
Xingchao
X
Wang
Neural Reconstructional Department, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (F.Z., J.Z., P.L.); Department of Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (L.L.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (F.Z., C.L., P.L., Z.Y., B.W., X.W., Z.W., P.L.); Department of Imaging and Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (L.A.); Section of Molecular Pathology, International Agency for Research on Cancer, World Health Organization, Lyon, France (H.O.); Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (L.X.); Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy (F.G.).
Zhenmin
Z
Wang
Neural Reconstructional Department, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (F.Z., J.Z., P.L.); Department of Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (L.L.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (F.Z., C.L., P.L., Z.Y., B.W., X.W., Z.W., P.L.); Department of Imaging and Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (L.A.); Section of Molecular Pathology, International Agency for Research on Cancer, World Health Organization, Lyon, France (H.O.); Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (L.X.); Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy (F.G.).
Lin
L
Ai
Neural Reconstructional Department, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (F.Z., J.Z., P.L.); Department of Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (L.L.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (F.Z., C.L., P.L., Z.Y., B.W., X.W., Z.W., P.L.); Department of Imaging and Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (L.A.); Section of Molecular Pathology, International Agency for Research on Cancer, World Health Organization, Lyon, France (H.O.); Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (L.X.); Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy (F.G.).
Jing
J
Zhang
Neural Reconstructional Department, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (F.Z., J.Z., P.L.); Department of Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (L.L.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (F.Z., C.L., P.L., Z.Y., B.W., X.W., Z.W., P.L.); Department of Imaging and Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (L.A.); Section of Molecular Pathology, International Agency for Research on Cancer, World Health Organization, Lyon, France (H.O.); Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (L.X.); Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy (F.G.).
Lin
L
Luo
Neural Reconstructional Department, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (F.Z., J.Z., P.L.); Department of Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China (L.L.); Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (F.Z., C.L., P.L., Z.Y., B.W., X.W., Z.W., P.L.); Department of Imaging and Nuclear Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (L.A.); Section of Molecular Pathology, International Agency for Research on Cancer, World Health Organization, Lyon, France (H.O.); Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (L.X.); Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy (F.G.).
Pinan
P
Liu
D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics; D002528:Cerebellar Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008527:Medulloblastoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D051153:Wnt Proteins / Q000378:metabolism; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism
D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D053823:Hedgehog Proteins; D051153:Wnt Proteins; D051176:beta Catenin
adult medulloblastoma; histology; molecular subgroup; prognosis; survival