Produção Nacional
Revisado por pares
Subgroup and subtype-specific outcomes in adult medulloblastoma
2021; Springer Science+Business Media; Volume: 142; Issue: 5 Linguagem: Inglês
10.1007/s00401-021-02358-4
ISSN1432-0533
AutoresHallie Coltin, Lakshmikirupa Sundaresan, Kyle Smith, Patryk Skowron, Luca Massimi, Charles G. Eberhart, Karisa C. Schreck, Nalin Gupta, William A. Weiss, Daniela Pretti da Cunha Tirapelli, Carlos Gilberto Carlotti, Kay K. W. Li, Marina Ryzhova, Andrey Golanov, Olga Zheludkova, O V Absalyamova, Konstantin Okonechnikov, Damian Stichel, Andreas von Deimling, Caterina Giannini, Scott Raskin, Erwin G. Van Meir, Jennifer A. Chan, Daniel W. Fults, Lola B. Chambless, Seung-Ki Kim, Alexandre Vasiljevic, Cécile Faure‐Conter, Rajeev Vibhakar, Shin Jung, Sarah Leary, Jaume Mora, Roger E. McLendon, Ian F. Pollack, Péter Hauser, Wiesława Grajkowska, Joshua B. Rubin, Marie‐Lise C. van Veelen, Pim J. French, Johan M. Kros, Linda M. Liau, Stefan M. Pfister, Marcel Kool, Noriyuki Kijima, Michael D. Taylor, Roger J. Packer, Paul A. Northcott, Andrey Korshunov, Vijay Ramaswamy,
Tópico(s)Chromatin Remodeling and Cancer
ResumoMedulloblastoma, 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.
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