Subgroup and subtype-specific outcomes in adult medulloblastoma.

Autor: Coltin H; Division of Haematology/Oncology, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada.; Programme in Developmental and Stem Cell Biology, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada., Sundaresan L; Programme in Developmental and Stem Cell Biology, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada., Smith KS; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, MS 325, Room D2058, 262 Danny Thomas Place, Memphis, TN, 38105-3678, USA., Skowron P; Programme in Developmental and Stem Cell Biology, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada., Massimi L; Department of Neurosurgery, Fondazione Policlinico A. Gemelli IRCCS, Catholic University Medical School, Rome, Italy., Eberhart CG; Department of Neuropathology and Ophthalmic Pathology, Johns Hopkins University, Baltimore, MD, USA., Schreck KC; Department of Neurology, Johns Hopkins University, Baltimore, MD, USA., Gupta N; Departments of Neurological Surgery and Pediatrics, University of California, San Francisco, CA, USA., Weiss WA; Departments of Neurology, Neurological Surgery, and Pediatrics, University of California, San Francisco, CA, USA., Tirapelli D; Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, University of Sao Paulo, São Paulo, Brazil., Carlotti C; Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, University of Sao Paulo, São Paulo, Brazil., Li KKW; Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong., Ryzhova M; NN Burdenko Neurosurgical Research Centre, Moscow, Russia., Golanov A; NN Burdenko Neurosurgical Research Centre, Moscow, Russia., Zheludkova O; NN Burdenko Neurosurgical Research Centre, Moscow, Russia., Absalyamova O; NN Burdenko Neurosurgical Research Centre, Moscow, Russia., Okonechnikov K; Hopp Children's Cancer Center Heidelberg (KiTZ) and Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Stichel D; Clinical Cooperation Unit Neuropathology (B300), German Cancer Research Center (DKFZ) and Department of Neuropathology, University of Heidelberg, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany., von Deimling A; Clinical Cooperation Unit Neuropathology (B300), German Cancer Research Center (DKFZ) and Department of Neuropathology, University of Heidelberg, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany., Giannini C; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., Raskin S; Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC, USA., Van Meir EG; Department of Neurosurgery, O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham (UAB), Birmingham, AL, USA., Chan JA; Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada., Fults D; Department of Neurosurgery, University of Utah, Salt Lake City, UT, USA., Chambless LB; Department of Neurological Surgery, Vanderbilt Medical Center, Nashville, TN, USA., Kim SK; Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul, South Korea., Vasiljevic A; Centre de Pathologie et Neuropathologie Est, Centre de Biologie et Pathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France.; ONCOFLAM, Neuro-Oncologie Et Neuro-Inflammation Centre de Recherche en Neurosciences de Lyon, Lyon, France., Faure-Conter C; Department of Pediatrics, Institut d'Hemato-Oncologie Pediatrique, Lyon, France., Vibhakar R; Department of Pediatrics, University of Colorado Denver, Aurora, CO, USA., Jung S; Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, Hwasun-gun, Chonnam, South Korea., Leary S; Cancer and Blood Disorders Center, Seattle Children's Hospital, Seattle, WA, USA., Mora J; Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain., McLendon RE; Department of Pathology, Duke University, Durham, NC, USA., Pollack IF; Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Hauser P; 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary., Grajkowska WA; Department of Pathology, The Children's Memorial Health Institute, Warsaw, Poland., Rubin JB; Departments of Pediatrics, Anatomy and Neurobiology, Washington University School of Medicine and St Louis Children's Hospital, St Louis, MO, USA., van Veelen MC; Department of Neurosurgery, Brain Tumour Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., French PJ; Department of Neurology, Brain Tumour Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Kros JM; Department of Pathology, Erasmus University Medical Center, Rotterdam, Netherlands., Liau LM; Department of Neurosurgery, David Geffen School of Medicine at University of California at Los Angeles, University of California Los Angeles, Los Angeles, CA, 90095, USA., Pfister SM; Hopp Children's Cancer Center Heidelberg (KiTZ) and Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany., Kool M; Hopp Children's Cancer Center Heidelberg (KiTZ) and Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Kijima N; Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Japan., Taylor MD; Programme in Developmental and Stem Cell Biology, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada., Packer RJ; Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC, USA., Northcott PA; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, MS 325, Room D2058, 262 Danny Thomas Place, Memphis, TN, 38105-3678, USA. paul.northcott@stjude.org., Korshunov A; Clinical Cooperation Unit Neuropathology (B300), German Cancer Research Center (DKFZ) and Department of Neuropathology, University of Heidelberg, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany. andrey.korshunov@med.uni-heidelberg.de., Ramaswamy V; Division of Haematology/Oncology, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada. vijay.ramaswamy@sickkids.ca.; Programme in Developmental and Stem Cell Biology, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada. vijay.ramaswamy@sickkids.ca.; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada. vijay.ramaswamy@sickkids.ca.
Jazyk: angličtina
Zdroj: Acta neuropathologica [Acta Neuropathol] 2021 Nov; Vol. 142 (5), pp. 859-871. Date of Electronic Publication: 2021 Aug 18.
DOI: 10.1007/s00401-021-02358-4
Abstrakt: Medulloblastoma, a common pediatric malignant central nervous system tumour, represent a small proportion of brain tumours in adults. Previously it has been shown that in adults, Sonic Hedgehog (SHH)-activated tumours predominate, with Wingless-type (WNT) and Group 4 being less common, but molecular risk stratification remains a challenge. We performed an integrated analysis consisting of genome-wide methylation profiling, copy number profiling, somatic nucleotide variants and correlation of clinical variables across a cohort of 191 adult medulloblastoma cases identified through the Medulloblastoma Advanced Genomics International Consortium. We identified 30 WNT, 112 SHH, 6 Group 3, and 41 Group 4 tumours. Patients with SHH tumours were significantly older at diagnosis compared to other subgroups (p < 0.0001). Five-year progression-free survival (PFS) for WNT, SHH, Group 3, and Group 4 tumours was 64.4 (48.0-86.5), 61.9% (51.6-74.2), 80.0% (95% CI 51.6-100.0), and 44.9% (95% CI 28.6-70.7), respectively (p = 0.06). None of the clinical variables (age, sex, metastatic status, extent of resection, chemotherapy, radiotherapy) were associated with subgroup-specific PFS. Survival among patients with SHH tumours was significantly worse for cases with chromosome 3p loss (HR 2.9, 95% CI 1.1-7.6; p = 0.02), chromosome 10q loss (HR 4.6, 95% CI 2.3-9.4; p < 0.0001), chromosome 17p loss (HR 2.3, 95% CI 1.1-4.8; p = 0.02), and PTCH1 mutations (HR 2.6, 95% CI 1.1-6.2; p = 0.04). The prognostic significance of 3p loss and 10q loss persisted in multivariable regression models. For Group 4 tumours, chromosome 8 loss was strongly associated with improved survival, which was validated in a non-overlapping cohort (combined cohort HR 0.2, 95% CI 0.1-0.7; p = 0.007). Unlike in pediatric medulloblastoma, whole chromosome 11 loss in Group 4 and chromosome 14q loss in SHH was not associated with improved survival, where MYCN, GLI2 and MYC amplification were rare. In sum, we report unique subgroup-specific cytogenetic features of adult medulloblastoma, which are distinct from those in younger patients, and correlate with survival disparities. Our findings suggest that clinical trials that incorporate new strategies tailored to high-risk adult medulloblastoma patients are urgently needed.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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