Advertisement

Next-generation whole exome sequencing of glioblastoma with a primitive neuronal component

  • Guiyan Xu
  • Hongwu Zheng
  • Jian Yi LiEmail author
Rapid Short communication
  • 32 Downloads

Abstract

Glioblastoma with a primitive neuronal component (GBM-PN) was renamed from glioblastoma with primitive neuroectodermal tumor-like component (GBM-PNET) in the new WHO classification of tumors of the central nervous system in 2016. GBM-PN is a rare variant of glioblastoma. There were not so many publications on the investigation of GBM-PN. We did whole exome sequencing for 11 GBM-PN cases and found that the percentage of TP53, PIK3CA, PIK3R1, or PTEN mutation in our GBM-PN cases (72.7%, 27.3%, 27.3%, and 27.3% respectively) was much higher than that in cases in TCGA GBM 2008, TCGA GBM 2013, and TCGA lower-grade glioma databases. The findings indicate that GBM-PN is a distinct variant of glioblastoma. The next-generation sequencing can play a role in the diagnosis of GBM-PN especially for small biopsy cases. Eight out of 11 cases showed mutations in PTEN–PI3K pathway, which indicates that targeted therapeutic agents (PI3K inhibitors, mTORC1 inhibitors or dual PI3K/mTOR inhibitors) may be used for the treatment of GBM-PN in the future.

Keywords

Glioblastoma with a primitive neuronal component (GBM-PN) Next-generation sequencing P53 PIK3CA PIK3R1 

Notes

Acknowledgements

We give special thanks to Dr. Betty Diamond, who provided the lab space and equipments. We also appreciate help and support from all her lab members. We are thankful for Mr. Daniel Loen and Ms. Jill Wishinsky for managing the Grant. Dept. of Pathology and Lab. Medicine: we thank Dr. James Crawford for his support and encouragement, Ms. Claudine Alexis for ordering all our materials, and people in histology laboratory and immunostain laboratory for technical support. Dr. Guiyan Xu now stays at home.

Funding

This work was supported by Northwell Health Cancer Institute.

Compliance with ethical standards

Conflict of interest

There is no conflict of interest.

References

  1. 1.
    Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D (2016) The 2016 world health organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820CrossRefGoogle Scholar
  2. 2.
    Perry A, Miller CR, Gujrati M, Scheithauer BW, Zambrano SC, Jost SC, Raghavan R, Qian J, Cochran EJ, Huse JT, Holland EC, Burger PC, Rosenblum MK (2009) Malignant gliomas with primitive neuroectodermal tumor-like components: a clinicopathologic and genetic study of 53 cases. Brain Pathol 19:81–90CrossRefGoogle Scholar
  3. 3.
    Song X, Andrew AR, Terence DS, Fung KM, Farmer P, Gandhi S, Ranjan T, Demopoulos A, Symons M, Schulder M, Li JY (2011) Glioblastoma with PNET-like components has a higher frequency of isocitrate dehydrogenase 1 (IDH1) mutation and likely a better prognosis than primary glioblastoma. Int J Clin Exp Pathol 4:651–660Google Scholar
  4. 4.
    Ali S, Joseph NM, Perry A, Barajas RF Jr, Cha S (2014) Apparent diffusion coefficient in glioblastoma with PNET-like components, a GBM variant. J Neurooncol 119:353–360CrossRefGoogle Scholar
  5. 5.
    The Cancer Genome Atlas Research Network (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061–1068CrossRefGoogle Scholar
  6. 6.
    Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR, Cooper LA, Rheinbay E, Miller CR, Vitucci M, Morozova O, Robertson AG, Noushmehr H, Laird PW, Cherniack AD, Akbani R, Huse JT, Ciriello G, Poisson LM, Barnholtz-Sloan JS, Berger MS, Brennan C, Colen RR, Colman H, Flanders AE, Giannini C, Grifford M, Iavarone A, Jain R, Joseph I, Kim J, Kasaian K, Mikkelsen T, Murray BA, O’Neill BP, Pachter L, Parsons DW, Sougnez C, Sulman EP, Vandenberg SR, Van Meir EG, Von DA, Zhang H, CrainD Lau K, Mallery D, Morris S, Paulauskis J, Penny R, Shelton T, Sherman M, Yena P, Black A, Bowen J, Dicostanzo K, Gastier-Foster J, Leraas KM, Lichtenberg TM, Pierson CR, Ramirez NC, Taylor C, Weaver S, Wise L, Zmuda E, Davidsen T, Demchok JA, Eley G, Ferguson ML, Hutter CM, Mills Shaw KR, Ozenberger BA, Sheth M, Sofia HJ, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Ayala B, Baboud J, Chudamani S, Jensen MA, Liu J, Pihl T, Raman R, Wan Y, Wu Y, Ally A, Auman JT, Balasundaram M, Balu S, Baylin SB, Beroukhim R, Bootwalla MS, Bowlby R, Bristow CA, Brooks D, Butterfield Y, Carlsen R, Carter S, Chin L, Chu A, Chuah E, Cibulskis K, Clarke A, Coetzee SG, Dhalla N, Fennell T, Fisher S, Gabriel S, Getz G, Gibbs R, Guin R, Hadjipanayis A, Hayes DN, Hinoue T, Hoadley K, Holt RA, Hoyle AP, Jefferys SR, Jones S, Jones CD, Kucherlapati R, Lai PH, Lander E, Lee S, Lichtenstein L, Ma Y, Maglinte DT, Mahadeshwar HS, Marra MA, Mayo M, Meng S, Meyerson ML, Mieczkowski PA, Moore RA, Mose LE, Mungall AJ, Pantazi A, Parfenov M, Park PJ, Parker JS, Perou CM, Protopopov A, Ren X, Roach J, Sabedot TS, Schein J, Schumacher SE, Seidman JG, Seth S, Shen H, Simons JV, Sipahimalani P, Soloway MG, Song X, Sun H, Tabak B, Tam A, Tan D, Tang J, Thiessen N, Triche T Jr, Van Den Berg DJ, Veluvolu U, Waring S, Weisenberger DJ, Wilkerson MD, Wong T, Wu J, Xi L, Xu AW, Yang L, Zack TI, Zhang J, Aksoy BA, Arachchi H, Benz C, Bernard B, Carlin D, Cho J, DiCara D, Frazer S, Fuller GN, Gao J, Gehlenborg N, Haussler D, Heiman DI, Iype L, Jacobsen A, Ju Z, Katzman S, Kim H, Knijnenburg T, Kreisberg RB, Lawrence MS, Lee W, Leinonen K, Lin P, Lind S, Liu W, Liu Y, Liu Y, Lu Y, Mills G, Ng S, Noble MS, Paull E, Rao A, Reynolds S, Saksena G, Sanborn Z, Sander C, Schultz N, Senbabaoglu Y, Shen R, Shmulevich I, Sinha R, Stuart J, Sumer SO, Sun Y, Tasman N, Taylor BS, Voet D, Weinhold N, Weinstein JN, Yang D, Yoshihara K, Zheng S, Zhang W, Zou L, Abel T, Sadeghi S, Cohen ML, Eschbacher J, Hattab EM, Raghunathan A, Schniederjan MJ, Aziz D, Barnett G, Barrett W, Bigner DD, Boice L, Brewer C, Calatozzolo C, Campos B, Carlotti CG Jr, Chan TA, Cuppini L, Curley E, Cuzzubbo S, Devine K, DiMeco F, Duell R, Elder JB, Fehrenbach A, Finocchiaro G (2015) Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 372:2481–2498CrossRefGoogle Scholar
  7. 7.
    Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR, Cooper LA, Rheinbay E, Miller CR, Vitucci M, Morozova O, Robertson AG, Noushmehr H, Laird PW, Cherniack AD, Akbani R, Huse JT, Ciriello G, Poisson LM, Barnholtz-Sloan JS, Berger MS, Brennan C, Colen RR, Colman H, Flanders AE, Giannini C, Grifford M, Iavarone A, Jain R, Joseph I, Kim J, Kasaian K, Mikkelsen T, Murray BA, O’Neill BP, Pachter L, Parsons DW, Sougnez C, Sulman EP, Vandenberg SR, Van Meir EG,Von DA, Zhang H, CrainD, Lau K, Mallery D, Morris S, Paulauskis J, Penny R, Shelton T, Sherman M, Yena P, Black A, Bowen J, Dicostanzo K, Gastier-Foster J, Leraas KM,Lichtenberg TM, Pierson CR, Ramirez NC, Taylor C, Weaver S, Wise L, Zmuda E, Davidsen T, Demchok JA, Eley G, Ferguson ML, Hutter CM, Mills Shaw KR, Ozenberger BA, Sheth M, Sofia HJ, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Ayala B, Baboud J,Chudamani S, Jensen MA, Liu J, Pihl T, Raman R, Wan Y, Wu Y, Ally A, Auman JT,Balasundaram M,Balu S, Baylin SB, Beroukhim R, Bootwalla MS, Bowlby R, Bristow CA,Brooks D, Butterfield Y, Carlsen R, Carter S, Chin L, Chu A, Chuah E, Cibulskis K, Clarke A, Coetzee SG,Dhalla N, Fennell T, Fisher S, Gabriel S, Getz G, Gibbs R, Guin R, Hadjipanayis A,Hayes DN, Hinoue T, Hoadley K, Holt RA, Hoyle AP, Jefferys SR, Jones S, Jones CD,Kucherlapati R, Lai PH, Lander E, Lee S, Lichtenstein L, Ma Y, Maglinte DT, Mahadeshwar HS, Marra MA, Mayo M, Meng S Meyerson ML, Mieczkowski PA, Moore RA, Mose LE, Mungall AJ, Pantazi A Parfenov M, Park PJ, Parker JS, Perou CM, Protopopov A, Ren X, Roach J Sabedot TS, Schein J, Schumacher SE, Seidman JG, Seth S, Shen H, Simons JV Sipahimalani P, Soloway MG, Song X, Sun H, Tabak B, Tam A, Tan D, Tang J Thiessen N, Triche T,Jr, Van Den Berg DJ, Veluvolu U, Waring S, Weisenberger DJ Wilkerson MD, Wong T, Wu J, Xi L, Xu AW, Yang L, Zack TI, Zhang J, Aksoy BA Arachchi H, Benz C, Bernard B,Carlin D, Cho J, DiCara D, Frazer S, Fuller GN, Gao J, Gehlenborg N, Haussler D, Heiman DI, Iype L, Jacobsen A, Ju Z, Katzman S, Kim H, Knijnenburg T, Kreisberg RB, Lawrence MS, Lee W, Leinonen K, Lin P Ling S, Liu W, Liu Y, Liu Y, Lu Y, Mills G, Ng S, Noble MS, Paull E, Rao A, Reynolds S, Saksena G, Sanborn Z, Sander C, Schultz N, Senbabaoglu Y, Shen R Shmulevich I, Sinha R, Stuart J, Sumer SO, Sun Y, Tasman N, Taylor BS, Voet D Weinhold N, Weinstein JN, Yang D, Yoshihara K, Zheng S, Zhang W, Zou L, Abel T Sadeghi S, Cohen ML, Eschbacher J, Hattab EM, Raghunathan A, Schniederjan MJ Aziz D, Barnett G, Barrett W, Bigner DD, Boice L, Brewer C, Calatozzolo C, Campos B, Carlotti CG,Jr, Chan TA, Cuppini L, Curley E, Cuzzubbo S, Devine K DiMeco F, Duell R, Elder JB,Fehrenbach A, Finocchiaro G (2015) Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 372:2481–2498CrossRefGoogle Scholar
  8. 8.
    Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C, Schultz N (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2:401–404CrossRefGoogle Scholar
  9. 9.
    Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Cerami E, Larsson E, Sander C, Schultz N (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 6:l1CrossRefGoogle Scholar

Copyright information

© The Japan Society of Brain Tumor Pathology 2019

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicineNorth Shore University Hospital and Long Island Jewish Medical CenterLake SuccessUSA
  2. 2.Cancer Institute, Northwell Health, Lake SuccessDonald and Barbara Zucker School of Medicine at Hofstra/NorthwellHempsteadUSA
  3. 3.Department of Pathology and Laboratory MedicineWeill Cornell Medicine CollegeNew YorkUSA

Personalised recommendations