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Integrated proteogenomic characterization of glioblastoma evolution.
Kim, Kyung-Hee; Migliozzi, Simona; Koo, Harim; Hong, Jun-Hee; Park, Seung Min; Kim, Sooheon; Kwon, Hyung Joon; Ha, Seokjun; Garofano, Luciano; Oh, Young Taek; D'Angelo, Fulvio; Kim, Chan Il; Kim, Seongsoo; Lee, Ji Yoon; Kim, Jiwon; Hong, Jisoo; Jang, Eun-Hae; Mathon, Bertrand; Di Stefano, Anna-Luisa; Bielle, Franck; Laurenge, Alice; Nesvizhskii, Alexey I; Hur, Eun-Mi; Yin, Jinlong; Shi, Bingyang; Kim, Youngwook; Moon, Kyung-Sub; Kwon, Jeong Taik; Lee, Shin Heon; Lee, Seung Hoon; Gwak, Ho Shin; Lasorella, Anna; Yoo, Heon; Sanson, Marc; Sa, Jason K; Park, Chul-Kee; Nam, Do-Hyun; Iavarone, Antonio; Park, Jong Bae.
Affiliation
  • Kim KH; Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea; Proteomics Core Facility, Research Core Center, Research Institute, National Cancer Center, Goyang, Korea.
  • Migliozzi S; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Koo H; Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea; Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Korea; Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Kore
  • Hong JH; Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
  • Park SM; Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
  • Kim S; Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
  • Kwon HJ; Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
  • Ha S; Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
  • Garofano L; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Oh YT; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
  • D'Angelo F; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Kim CI; Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
  • Kim S; Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
  • Lee JY; Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Korea; Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Korea.
  • Kim J; Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Korea; Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Korea.
  • Hong J; Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Korea; Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Korea.
  • Jang EH; Laboratory of Neuroscience, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea.
  • Mathon B; Service de Neurochirurgie, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Paris, France.
  • Di Stefano AL; Institut de Neurologie, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Paris, France; Sorbonne Université, Inserm, CNRS, UMR S 1127, Paris Brain Institute (ICM), Equipe labellisée LNCC, Paris, France; Onconeurotek, AP-HP, Hôpital Pitié-Salpêtrière, F-75013 Paris, France; Departm
  • Bielle F; Institut de Neurologie, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Paris, France; Sorbonne Université, Inserm, CNRS, UMR S 1127, Paris Brain Institute (ICM), Equipe labellisée LNCC, Paris, France; Onconeurotek, AP-HP, Hôpital Pitié-Salpêtrière, F-75013 Paris, France.
  • Laurenge A; Institut de Neurologie, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Paris, France; Sorbonne Université, Inserm, CNRS, UMR S 1127, Paris Brain Institute (ICM), Equipe labellisée LNCC, Paris, France; Onconeurotek, AP-HP, Hôpital Pitié-Salpêtrière, F-75013 Paris, France.
  • Nesvizhskii AI; Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Hur EM; Laboratory of Neuroscience, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea; BK21 Four Future Veterinary Medicine Leading Education & Research Center, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
  • Yin J; Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea; Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan, China.
  • Shi B; Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan, China.
  • Kim Y; Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
  • Moon KS; Department of Neurosurgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Korea.
  • Kwon JT; Department of Neurosurgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
  • Lee SH; Department of Neurosurgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
  • Lee SH; Department of Neurosurgery, Eulji University School of Medicine, Daejeon, Korea.
  • Gwak HS; Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
  • Lasorella A; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Biochemistry, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Yoo H; Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
  • Sanson M; Institut de Neurologie, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Paris, France; Sorbonne Université, Inserm, CNRS, UMR S 1127, Paris Brain Institute (ICM), Equipe labellisée LNCC, Paris, France; Onconeurotek, AP-HP, Hôpital Pitié-Salpêtrière, F-75013 Paris, France. Electro
  • Sa JK; Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Korea; Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Korea. Electronic address: jasonksa@korea.ac.kr.
  • Park CK; Deparment of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea. Electronic address: nsckpark@snu.ac.kr.
  • Nam DH; Department of Neurosurgery and Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Electronic address: nsnam@skku.edu.
  • Iavarone A; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Neurological Surgery and Department of Biochemistry, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: axi435@med.miami.edu.
  • Park JB; Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea; Department of Clinical Research, Research Institute and Hospital, National Cancer Center, Goyang, Korea. Electronic address: jbp@ncc.re.kr.
Cancer Cell ; 42(3): 358-377.e8, 2024 Mar 11.
Article in En | MEDLINE | ID: mdl-38215747
ABSTRACT
The evolutionary trajectory of glioblastoma (GBM) is a multifaceted biological process that extends beyond genetic alterations alone. Here, we perform an integrative proteogenomic analysis of 123 longitudinal glioblastoma pairs and identify a highly proliferative cellular state at diagnosis and replacement by activation of neuronal transition and synaptogenic pathways in recurrent tumors. Proteomic and phosphoproteomic analyses reveal that the molecular transition to neuronal state at recurrence is marked by post-translational activation of the wingless-related integration site (WNT)/ planar cell polarity (PCP) signaling pathway and BRAF protein kinase. Consistently, multi-omic analysis of patient-derived xenograft (PDX) models mirror similar patterns of evolutionary trajectory. Inhibition of B-raf proto-oncogene (BRAF) kinase impairs both neuronal transition and migration capability of recurrent tumor cells, phenotypic hallmarks of post-therapy progression. Combinatorial treatment of temozolomide (TMZ) with BRAF inhibitor, vemurafenib, significantly extends the survival of PDX models. This study provides comprehensive insights into the biological mechanisms of glioblastoma evolution and treatment resistance, highlighting promising therapeutic strategies for clinical intervention.
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Full text: 1 Database: MEDLINE Main subject: Brain Neoplasms / Glioblastoma / Proteogenomics Limits: Animals / Humans Language: En Year: 2024 Type: Article
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Full text: 1 Database: MEDLINE Main subject: Brain Neoplasms / Glioblastoma / Proteogenomics Limits: Animals / Humans Language: En Year: 2024 Type: Article