المؤلفون: Shi, Zhi-Feng, Li, Kay Ka-Wai, Chan, Danny Tat-Ming, Mao, Ying, Ng, Ho-Keung

المساهمون: National Natural Science Foundation of China, Shanghai Youth Science and Technology Bright Star Program, Shanghai Municipal Health Commission Outstanding Project

المصدر: Neuro-Oncology Advances ; volume 6, issue 1 ; ISSN 2632-2498

مصطلحات موضوعية: Surgery, Oncology, Neurology (clinical)

الإتاحة: https://doi.org/10.1093/noajnl/vdae006Test
https://academic.oup.com/noa/article-pdf/6/1/vdae006/56691449/vdae006.pdfTest

المؤلفون: Skowron, Patryk, Farooq, Hamza, Cavalli, Florence MG, Morrissy, A Sorana, Ly, Michelle, Hendrikse, Liam D, Wang, Evan Y, Djambazian, Haig, Zhu, Helen, Mungall, Karen L, Trinh, Quang M, Zheng, Tina, Dai, Shizhong, Stucklin, Ana S Guerreiro, Vladoiu, Maria C, Fong, Vernon, Holgado, Borja L, Nor, Carolina, Wu, Xiaochong, Abd-Rabbo, Diala, Bérubé, Pierre, Wang, Yu Chang, Luu, Betty, Suarez, Raul A, Rastan, Avesta, Gillmor, Aaron H, Lee, John JY, Zhang, Xiao Yun, Daniels, Craig, Dirks, Peter, Malkin, David, Bouffet, Eric, Tabori, Uri, Loukides, James, Doz, François P, Bourdeaut, Franck, Delattre, Olivier O, Masliah-Planchon, Julien, Ayrault, Olivier, Kim, Seung-Ki, Meyronet, David, Grajkowska, Wieslawa A, Carlotti, Carlos G, de Torres, Carmen, Mora, Jaume, Eberhart, Charles G, Van Meir, Erwin G, Kumabe, Toshihiro, French, Pim J, Kros, Johan M, Jabado, Nada, Lach, Boleslaw, Pollack, Ian F, Hamilton, Ronald L, Rao, Amulya A Nageswara, Giannini, Caterina, Olson, James M, Bognár, László, Klekner, Almos, Zitterbart, Karel, Phillips, Joanna J, Thompson, Reid C, Cooper, Michael K, Rubin, Joshua B, Liau, Linda M, Garami, Miklós, Hauser, Peter, Li, Kay Ka Wai, Ng, Ho-Keung, Poon, Wai Sang, Yancey Gillespie, G, Chan, Jennifer A, Jung, Shin, McLendon, Roger E, Thompson, Eric M, Zagzag, David, Vibhakar, Rajeev, Ra, Young Shin, Garre, Maria Luisa, Schüller, Ulrich, Shofuda, Tomoko, Faria, Claudia C, López-Aguilar, Enrique, Zadeh, Gelareh, Hui, Chi-Chung, Ramaswamy, Vijay, Bailey, Swneke D, Jones, Steven J, Mungall, Andrew J, Moore, Richard A, Calarco, John A, Stein, Lincoln D, Bader, Gary D, Reimand, Jüri, Ragoussis, Jiannis, Weiss, William A, Marra, Marco A, Suzuki, Hiromichi, Taylor, Michael D

المصدر: Nature communications. 12(1)

مصطلحات موضوعية: Humans, Medulloblastoma, Cerebellar Neoplasms, Signal Transduction, Gene Expression Regulation, Neoplastic, Adolescent, Adult, Middle Aged, Child, Child, Preschool, Infant, Female, Male, Hedgehog Proteins, Gene Regulatory Networks, Genetic Variation, Young Adult, Transcriptome, Pediatric Research Initiative, Brain Cancer, Pediatric, Rare Diseases, Genetics, Pediatric Cancer, Clinical Research, Brain Disorders, Neurosciences, Biotechnology, Human Genome, Cancer, 2.1 Biological and endogenous factors

الوصف: Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8726s0hdTest

المؤلفون: Nobre, Liana, Zapotocky, Michal, Khan, Sara, Fukuoka, Kohei, Fonseca, Adriana, McKeown, Tara, Sumerauer, David, Vicha, Ales, Grajkowska, Wieslawa A, Trubicka, Joanna, Li, Kay Ka Wai, Ng, Ho-Keung, Massimi, Luca, Lee, Ji Yeoun, Kim, Seung-Ki, Zelcer, Shayna, Vasiljevic, Alexandre, Faure-Conter, Cécile, Hauser, Peter, Lach, Boleslaw, van Veelen-Vincent, Marie-Lise, French, Pim J, Van Meir, Erwin G, Weiss, William A, Gupta, Nalin, Pollack, Ian F, Hamilton, Ronald L, Rao, Amulya A Nageswara, Giannini, Caterina, Rubin, Joshua B, Moore, Andrew S, Chambless, Lola B, Vibhakar, Rajeev, Ra, Young Shin, Massimino, Maura, McLendon, Roger E, Wheeler, Helen, Zollo, Massimo, Ferruci, Veronica, Kumabe, Toshihiro, Faria, Claudia C, Sterba, Jaroslav, Jung, Shin, López-Aguilar, Enrique, Mora, Jaume, Carlotti, Carlos G, Olson, James M, Leary, Sarah, Cain, Jason, Krskova, Lenka, Zamecnik, Josef, Hawkins, Cynthia E, Tabori, Uri, Huang, Annie, Bartels, Ute, Northcott, Paul A, Taylor, Michael D, Yip, Stephen, Hansford, Jordan R, Bouffet, Eric, Ramaswamy, Vijay

المصدر: Cell Reports Medicine. 1(3)

مصطلحات موضوعية: Cancer, Clinical Research, Evaluation of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Adolescent, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Cerebellar Neoplasms, Child, Cyclophosphamide, Female, Humans, Ifosfamide, Male, Medulloblastoma, Middle Aged, Neoplasm Recurrence, Local, Progression-Free Survival, medulloblastoma, WNT, genomics, cyclophosphamide, chemotherapy, prognosis, survival

الوصف: Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/462693g4Test

المؤلفون: Shi, Zhi-Feng^1,2 (AUTHOR) shizhifeng@fudan.edu.cn, Li, Kay Ka-Wai³ (AUTHOR) kayli@cuhk.edu.hk, Liu, Anthony Pak-Yin^4,5 (AUTHOR), Chung, Nellie Yuk-Fei³ (AUTHOR) yf169chung@cuhk.edu.hk, Wong, Sze-Ching³ (AUTHOR) scwong@cuhk.edu.hk, Chen, Hong⁶ (AUTHOR) cherrychen30@126.com, Woo, Peter Yat-Ming⁷ (AUTHOR) peterwoo@surgery.cuhk.edu.hk, Chan, Danny Tat-Ming⁷ (AUTHOR) tmdanny@surgery.cuhk.edu.hk, Mao, Ying^1,2 (AUTHOR) maoying@fudan.edu.cn, Ng, Ho-Keung^2,3 (AUTHOR) maoying@fudan.edu.cn

المصدر: Cancers. May2024, Vol. 16 Issue 9, p1740. 15p.

مصطلحات موضوعية: *GENE rearrangement, *LYMPHOMAS, *SYMPTOMS, *AGE distribution, *DESCRIPTIVE statistics, *GENE expression, *GENE expression profiling, *FLUORESCENCE in situ hybridization, *GENETIC mutation, *PHENOTYPES, *HLA-B27 antigen, *IMMUNOMODULATORS, *SEQUENCE analysis, *CHILDREN, *ADULTS, CENTRAL nervous system tumors

مستخلص: Simple Summary: Primary CNS lymphomas (PCNSLs) in children and young adults are not common. In this study, we studied immunophenotype, gene rearrangement, homozygous deletion of CDKN2A and HLA, and mutation profiling of 34 PCNSL patients aged between 7 and 39 years and correlated the findings with clinical features and outcome. We found that the PCNSLs of the pediatric and young adult patients were immunophenotypically different from the PCNSLs of the older patients. They were also molecularly different from the latter group, as many of the common molecular findings identified in the latter were not present or common in the PCNSLs of the pediatric and young adult patients. Pediatric brain tumors are often noted to be different from their adult counterparts in terms of molecular features. Primary CNS lymphomas (PCNSLs) are mostly found in elderly adults and are uncommon in children and teenagers. There has only been scanty information about the molecular features of PCNSLs at a young age. We examined PCNSLs in 34 young patients aged between 7 and 39 years for gene rearrangements of BCl2, BCL6, CCND1, IRF4, IGH, IGL, IGK, and MYC, homozygous deletions (HD) of CDKN2A, and HLA by FISH. Sequencing was performed using WES, panel target sequencing, or Sanger sequencing due to the small amount of available tissues. The median OS was 97.5 months and longer than that for older patients with PCNSLs. Overall, only 14 instances of gene rearrangement were found (5%), and patients with any gene rearrangement were significantly older (p = 0.029). CDKN2A HD was associated with a shorter OS (p < 0.001). Only 10/31 (32%) showed MYD88 mutations, which were not prognostically significant, and only three of them were L265P mutations. CARD11 mutations were found in 8/24 (33%) cases only. Immunophenotypically, the cases were predominantly GCB, in contrast to older adults (61%). In summary, we showed that molecular findings identified in the PCNSLs of the older patients were only sparingly present in pediatric and young adult patients. [ABSTRACT FROM AUTHOR]

المؤلفون: Cavalli, Florence MG, Remke, Marc, Rampasek, Ladislav, Peacock, John, Shih, David JH, Luu, Betty, Garzia, Livia, Torchia, Jonathon, Nor, Carolina, Morrissy, A Sorana, Agnihotri, Sameer, Thompson, Yuan Yao, Kuzan-Fischer, Claudia M, Farooq, Hamza, Isaev, Keren, Daniels, Craig, Cho, Byung-Kyu, Kim, Seung-Ki, Wang, Kyu-Chang, Lee, Ji Yeoun, Grajkowska, Wieslawa A, Perek-Polnik, Marta, Vasiljevic, Alexandre, Faure-Conter, Cecile, Jouvet, Anne, Giannini, Caterina, Rao, Amulya A Nageswara, Li, Kay Ka Wai, Ng, Ho-Keung, Eberhart, Charles G, Pollack, Ian F, Hamilton, Ronald L, Gillespie, G Yancey, Olson, James M, Leary, Sarah, Weiss, William A, Lach, Boleslaw, Chambless, Lola B, Thompson, Reid C, Cooper, Michael K, Vibhakar, Rajeev, Hauser, Peter, van Veelen, Marie-Lise C, Kros, Johan M, French, Pim J, Ra, Young Shin, Kumabe, Toshihiro, López-Aguilar, Enrique, Zitterbart, Karel, Sterba, Jaroslav, Finocchiaro, Gaetano, Massimino, Maura, Van Meir, Erwin G, Osuka, Satoru, Shofuda, Tomoko, Klekner, Almos, Zollo, Massimo, Leonard, Jeffrey R, Rubin, Joshua B, Jabado, Nada, Albrecht, Steffen, Mora, Jaume, Van Meter, Timothy E, Jung, Shin, Moore, Andrew S, Hallahan, Andrew R, Chan, Jennifer A, Tirapelli, Daniela PC, Carlotti, Carlos G, Fouladi, Maryam, Pimentel, José, Faria, Claudia C, Saad, Ali G, Massimi, Luca, Liau, Linda M, Wheeler, Helen, Nakamura, Hideo, Elbabaa, Samer K, Perezpeña-Diazconti, Mario, de León, Fernando Chico Ponce, Robinson, Shenandoah, Zapotocky, Michal, Lassaletta, Alvaro, Huang, Annie, Hawkins, Cynthia E, Tabori, Uri, Bouffet, Eric, Bartels, Ute, Dirks, Peter B, Rutka, James T, Bader, Gary D, Reimand, Jüri, Goldenberg, Anna, Ramaswamy, Vijay, Taylor, Michael D

المصدر: Cancer Cell. 31(6)

مصطلحات موضوعية: Genetics, Rare Diseases, Pediatric Cancer, Cancer, Brain Cancer, Pediatric Research Initiative, Pediatric, Human Genome, Brain Disorders, Cluster Analysis, Cohort Studies, DNA Copy Number Variations, DNA Methylation, Gene Expression Profiling, Genomics, Humans, Medulloblastoma, Precision Medicine, copy number, gene expression, integrative clustering, medulloblastoma, methylation, subgroups, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis

الوصف: While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/61b1617dTest

المؤلفون: Liu, Emma Munan, Shi, Zhi‐Feng, Li, Kay Ka‐Wai, Malta, Tathiane M., Chung, Nellie Yuk‐Fei, Chen, Hong, Chan, Janice Yuen‐Tung, Poon, Manix Fung‐Man, Kwan, Johnny Sheung‐Him, Chan, Danny Tat‐Ming, Noushmehr, Houtan, Mao, Ying, Ng, Ho‐Keung

المساهمون: National Natural Science Foundation of China, Food and Health Bureau, Health and Medical Research Fund

المصدر: Brain Pathology ; volume 32, issue 6 ; ISSN 1015-6305 1750-3639

الوصف: Telomerase reverse transcriptase ( TERT ) promoter (p TERT ) mutation has often been described as a late event in gliomagenesis and it has been suggested as a prognostic biomarker in gliomas other than 1p19q codeleted tumors. However, the characteristics of isocitrate dehydrogenase ( IDH ) wild type (wt) ( IDH wt), p TERT wt glioblastomas are not well known. We recruited 72 adult IDH wt, p TERT wt glioblastomas and performed methylation profiling, targeted sequencing, and fluorescence in situ hybridization (FISH) for TERT structural rearrangement and ALT (alternative lengthening of telomeres). There was no significant difference in overall survival (OS) between our cohort and a the Cancer Genome Atlas (TCGA) cohort of IDH wt, p TERT mutant (mut) glioblastomas, suggesting that p TERT mutation on its own is not a prognostic factor among IDH wt glioblastomas. Epigenetically, the tumors clustered into classic‐like (11%), mesenchymal‐like (32%), and LGm6‐glioblastoma (GBM) (57%), the latter far exceeding the corresponding proportion seen in the TCGA cohort of IDH wt, p TERT mut glioblastomas. LGm6‐GBM‐clustered tumors were enriched for platelet derived growth factor receptor alpha ( PDGFRA) amplification or mutation ( p = 0.008), and contained far fewer epidermal growth factor receptor ( EGFR ) amplification ( p < 0.01), 10p loss ( p = 0.001) and 10q loss ( p < 0.001) compared with cases not clustered to this group. LGm6‐GBM cases predominantly showed ALT ( p = 0.038). In the whole cohort, only 35% cases showed EGFR amplification and no case showed combined chromosome +7/−10. Since the cases were already p TERT wt, so the three molecular properties of EGFR amplification, +7/−10, and p TERT mutation may not cover all IDH wt glioblastomas. Instead, EGFR and PDGFRA amplifications covered 67% and together with their mutations covered 71% of cases of this cohort. Homozygous deletion of cyclin dependent kinase inhibitor 2A ( CDKN2A)/B was associated with a worse OS ( p = 0.031) and was an independent ...

الإتاحة: https://doi.org/10.1111/bpa.13107Test

المؤلفون: Ng, Ho‐Keung, Li, Kay Ka‐Wai, Chung, Nellie Yuk‐Fei, Chan, Janice Yuen‐Tung, Poon, Manix Fung‐Man, Wong, Queenie Hoi‐Wing, Kwan, Johnny Sheung‐Him, Poon, Wai‐Sang, Chen, Hong, Chan, Danny Tat‐Ming, Shi, Zhi‐Feng, Mao, Ying

المساهمون: National Natural Science Foundation of China

المصدر: Brain Pathology ; volume 33, issue 3 ; ISSN 1015-6305 1750-3639

الوصف: Recurrence is a major complication of some meningiomas. Although there were many studies on biomarkers associated with higher grades or increased aggressiveness, few studies specifically examined longitudinal samples of primary meningiomas and recurrences from the same patients for molecular life history. We studied 99 primary and recurrent meningiomas from 42 patients by FISH for 22q, 1q, 1p, 3p, 5q, 6q, 10p, 10q, 14q, 18q, CDKN2A/B homozygous deletion, ALT (Alternative Lengthening of Telomere), TERT re‐arrangement, targeted sequencing and TERT p sequencing. Although NF2 mutation and 22q were well known to be aetiological events in meningiomas, we found that in these paired meningiomas, combining the two events resulted in an NF2 /22q group (57 tumors from 25 patients) which were almost mutually exclusive with those cases without these two changes (42 tumors from 17 patients) for NF2 /22q. No other molecular changes were totally unique to NF2 /22q or non‐ NF2 /22q tumors. For molecular evolution, NF2 /22q meningiomas had higher cytogenetic abnormalities than non‐ NF2 /22q meningiomas ( p = 0.003). Most of the cytogenetic changes in NF2/ 22q meningiomas were present from the outset whereas for non‐ NF2 /22q meningiomas, cytogenetic events were uncommon in the primary tumors and most were acquired in recurrences. For non‐ NF2 /22q tumors, CDKN2A/B homozygous deletion, 1q gain, 18p loss, 3p loss, and ALT were preferentially found in recurrences. Mutations were largely conserved between primary and recurrent tumors. Phylogenetic trees showed 11/11 patients with multiple recurrent tumors had a conserved evolutionary pattern. We conclude that for molecular life history, NF2 and 22q should be regarded as a group. NF2 /22q recurring meningiomas showed more cytogenetic abnormalities in the primary tumors, whereas non‐ NF2 /22q meningiomas showed CDKN2A/B deletion and other cytogenetic abnormalities and ALT at recurrences. Although chromosome 1p loss is a known poor prognostic marker in meningiomas, it was also ...

الإتاحة: https://doi.org/10.1111/bpa.13120Test

المؤلفون: Pak-Yin Liu, Anthony, Li, Kay Ka-Wai, Chow, Chit, Chan, Shing, Leung, Alex Wing-Kwan, Shing, Matthew Ming-Kong, To, Ka-Fai, Chan, Danny Tat-Ming, Chan, Godfrey Chi-Fung, Ng, Ho-Keung

المصدر: Neuro-Oncology ; volume 24, issue Supplement_1, page i10-i10 ; ISSN 1522-8517 1523-5866

مصطلحات موضوعية: Cancer Research, Neurology (clinical), Oncology

الوصف: Pituitary blastomas (PitB) are rare DICER1-associated tumors that occur exclusively in children < 2 years of age. They are locally aggressive tumors that are driven by a combination of germline and somatic alterations involving DICER1. Here, we report two patients with pituitary neoplasms that expand the clinical and molecular spectrum of PitB. Patient 1 presented at 10 months with diabetes insipidus and was initially diagnosed with pituitary ependymoblastoma. She received debulking, chemotherapy and focal radiation with complete response achieved, but unfortunately died at the age of 8 years due to cerebral edema. Patient 2 was a survivor of infant leukemia who was treated with chemotherapy and then further chemotherapy with cranial irradiation at relapse. The patient was then diagnosed at the age of 8 years with pituitary CNS-PNET, which was treated with craniospinal irradiation and chemotherapy, and had remained in remission for 6 years. Review of histology in both cases indicates presence of neuroendocrine lobules, primitive cells, and Rathke pouch-like glandular structures, with high Ki67, ACTH and PRAME positivity compatible with PitB. Next-generation sequencing revealed presence of two DICER1 mutations (germline frameshifting and somatic missense) in Patient 1, and one somatic missense DICER1 mutation plus loss of heterozygosity in Patient 2 (no germline alteration). Surprisingly, C19MC amplification was also detected in Patient 1. Methylation profiling confirms clustering among our samples and PitB references, but not ETMR references. MicroRNA array revealed decrease in mature microRNA expression and preferential down-regulation of 5p/3p species in tumor compared to control pituitary tissue. In all, PitBs may present with clinical and molecular characteristics not conforming with the classical descriptions. It might be prudent to consider sequencing for DICER1 alteration in pediatric pituitary tumors to facilitate diagnosis of this increasingly heterogeneous rare entity.

الإتاحة: https://doi.org/10.1093/neuonc/noac079.031Test
https://academic.oup.com/neuro-oncology/article-pdf/24/Supplement_1/i10/43944833/noac079.031.pdfTest

المؤلفون: Chan, Aden Ka-Yin, Shi, Zhi-Feng, Li, Kay Ka-Wai, Wang, Wei-Wei, Chen, Hong, Chung, Nellie Yuk-Fei, Chan, Danny Tat-Ming, Poon, Wai-Sang, Loong, Herbert Ho-fung, Liu, Xian-Zhi, Zhang, Zhen-Yu, Mao, Ying, Ng, Ho-Keung

المساهمون: Health and Medical Research Fund, National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality

المصدر: Frontiers in Oncology ; volume 12 ; ISSN 2234-943X

مصطلحات موضوعية: Cancer Research, Oncology

الوصف: Advanced genomic techniques have now been incorporated into diagnostic practice in neuro-oncology in the literature. However, these assays are expensive and time-consuming and demand bioinformatics expertise for data interpretation. In contrast, single-gene tests can be run much more cheaply, with a short turnaround time, and are available in general pathology laboratories. The objective of this study was to establish a molecular grading scheme for adult gliomas using combinations of commonly available single-gene tests. We retrospectively evaluated molecular diagnostic data of 1,275 cases of adult diffuse gliomas from three institutions where we were testing for IDH1/2 mutation, TERTp mutation, 1p19q codeletion, EGFR amplification, 10q deletion, BRAF V600E, and H3 mutations liberally in our regular diagnostic workup. We found that a molecular grading scheme of Group 1 (1p19q codeleted, IDH mutant), Group 2 (IDH mutant, 1p19q non-deleted, TERT mutant), Group 3 (IDH mutant, 1p19q non-deleted, TERT wild type), Group 4 (IDH wild type, BRAF mutant), Group 5 (IDH wild type, BRAF wild type and not possessing the criteria of Group 6), and Group 6 (IDH wild type, and any one of TERT mutant, EGFR amplification, 10q deletion, or H3 mutant) could significantly stratify this large cohort of gliomas for risk. A total of 1,028 (80.6%) cases were thus classifiable with sufficient molecular data. There were 270 cases of molecular Group 1, 59 cases of molecular Group 2, 248 cases of molecular Group 3, 27 cases of molecular Group 4, 117 cases of molecular Group 5, and 307 cases of molecular Group 6. The molecular groups were independent prognosticators by multivariate analyses and in specific instances, superseded conventional histological grades. We were also able to validate the usefulness of the Groups with a cohort retrieved from The Cancer Genome Atlas (TCGA) where similar molecular tests were liberally available. We conclude that a single-gene molecular stratification system, useful for fine prognostication, is feasible and ...

الإتاحة: https://doi.org/10.3389/fonc.2022.839302Test

المؤلفون: Thompson, Eric M, Hielscher, Thomas, Bouffet, Eric, Remke, Marc, Luu, Betty, Gururangan, Sridharan, McLendon, Roger E, Bigner, Darell D, Lipp, Eric S, Perreault, Sebastien, Cho, Yoon-Jae, Grant, Gerald, Kim, Seung-Ki, Lee, Ji Yeoun, Rao, Amulya A Nageswara, Giannini, Caterina, Li, Kay Ka Wai, Ng, Ho-Keung, Yao, Yu, Kumabe, Toshihiro, Tominaga, Teiji, Grajkowska, Wieslawa A, Perek-Polnik, Marta, Low, David CY, Seow, Wan Tew, Chang, Kenneth TE, Mora, Jaume, Pollack, Ian F, Hamilton, Ronald L, Leary, Sarah, Moore, Andrew S, Ingram, Wendy J, Hallahan, Andrew R, Jouvet, Anne, Fèvre-Montange, Michelle, Vasiljevic, Alexandre, Faure-Conter, Cecile, Shofuda, Tomoko, Kagawa, Naoki, Hashimoto, Naoya, Jabado, Nada, Weil, Alexander G, Gayden, Tenzin, Wataya, Takafumi, Shalaby, Tarek, Grotzer, Michael, Zitterbart, Karel, Sterba, Jaroslav, Kren, Leos, Hortobágyi, Tibor, Klekner, Almos, László, Bognár, Pócza, Tímea, Hauser, Peter, Schüller, Ulrich, Jung, Shin, Jang, Woo-Youl, French, Pim J, Kros, Johan M, van Veelen, Marie-Lise C, Massimi, Luca, Leonard, Jeffrey R, Rubin, Joshua B, Vibhakar, Rajeev, Chambless, Lola B, Cooper, Michael K, Thompson, Reid C, Faria, Claudia C, Carvalho, Alice, Nunes, Sofia, Pimentel, José, Fan, Xing, Muraszko, Karin M, López-Aguilar, Enrique, Lyden, David, Garzia, Livia, Shih, David JH, Kijima, Noriyuki, Schneider, Christian, Adamski, Jennifer, Northcott, Paul A, Kool, Marcel, Jones, David TW, Chan, Jennifer A, Nikolic, Ana, Garre, Maria Luisa, Van Meir, Erwin G, Osuka, Satoru, Olson, Jeffrey J, Jahangiri, Arman, Castro, Brandyn A, Gupta, Nalin, Weiss, William A, Moxon-Emre, Iska, Mabbott, Donald J, Lassaletta, Alvaro, Hawkins, Cynthia E, Tabori, Uri, Drake, James, Kulkarni, Abhaya

المصدر: The Lancet Oncology. 17(4)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Oncology and Carcinogenesis, Brain Disorders, Rare Diseases, Brain Cancer, Pediatric Research Initiative, Pediatric, Cancer, Adult, Brain Neoplasms, Canada, Child, Child, Preschool, Combined Modality Therapy, Disease Progression, Disease-Free Survival, Female, Humans, Infant, Magnetic Resonance Imaging, Male, Medulloblastoma, Prognosis, Retrospective Studies, Oncology & Carcinogenesis, Oncology and carcinogenesis

الوصف: BackgroundPatients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner.MethodsWe retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival.FindingsWe included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1·45, 95% CI 1·07-1·96, p=0·16) but no overall survival benefit (HR 1·23, 0·87-1·72, p=0·24). We saw no progression-free survival or overall survival benefit for gross total resection compared with near-total resection (HR 1·05, 0·71-1·53, p=0·8158 for progression-free survival and HR 1·14, 0·75-1·72, p=0·55 for overall survival). No significant survival benefit existed for greater extent of resection for patients with WNT, SHH, or group 3 tumours (HR 1·03, 0·67-1·58, p=0·89 for sub-total resection vs gross total resection). For patients with group 4 tumours, gross total resection conferred a benefit to progression-free survival compared with sub-total resection (HR 1·97, 1·22-3·17, p=0·0056), especially for those with metastatic disease (HR 2·22, 1·00-4·93, p=0·050). However, gross total resection had no effect on overall survival compared with sub-total resection in patients with group 4 tumours (HR 1·67, 0·93-2·99, p=0·084).InterpretationThe prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. Although maximum safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high because there is no definitive benefit to gross total resection compared with near-total resection.FundingCanadian Cancer Society Research Institute, Terry Fox Research Institute, Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, and the Garron Family Chair in Childhood Cancer Research.

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الوصول الحر: https://escholarship.org/uc/item/93k1437dTest