Skip to main content
SpringerLink
Log in

Genomic analysis of synchronous intracranial meningiomas with different histological grades

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Although meningioma is the most common primary tumor of the central nervous system, the mechanism of progression from benign to atypical or anaplastic grade remains elusive. The present case reports the genomic evaluation of two synchronous meningiomas with different histological grades (benign and atypical) in the same patient. Under the assumption that the atypical tumor may have progressed from the benign tumor, the clonal origin of the lesions was investigated to identify genomic events responsible for the oncogenic process of evolution to higher grades in meningioma. A 59 year-old female patient was diagnosed with two synchronous meningiomas with different histological grades, benign and atypical. Whole-exome sequencing (WES) and RNA sequencing (RNA-seq) analysis of both tumors were done. WES analysis showed that each meningioma harbored distinct mutation profiles, and RNA-seq analysis revealed distinct gene expression profiles between the two tumors. The only apparent common genetic abnormality found in both tumors was the loss of heterozygosity of chromosome 22, raising the possibility that this event is the initial step in tumor formation, after which distinct subsequent mutations lead to the evolvement of two separate tumors of different grades. The result provides additional evidence on previous reports suggesting separate, independent mechanism of progression into higher grades in meningioma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Dolecek TA, Propp JM, Stroup NE, Kruchko C (2012) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro-Oncol 14(Suppl 5):v1–v49. https://doi.org/10.1093/neuonc/nos218

    Article  Google Scholar 

  2. Louis DN, Perry A, Reifenberger G, Deimling AV, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 world health organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131(6):803–820. https://doi.org/10.1007/s00401-016-1545-1

    Article  PubMed  Google Scholar 

  3. Zang KD (2001) Meningioma: a cytogenetic model of a complex benign human tumor, including data on 394 karyotyped cases. Cytogenet Cell Genet 93(3–4):207–220

    Article  CAS  PubMed  Google Scholar 

  4. Brastianos PK, Horowitz PM, Santagata S, Jones RT, McKenna A, Getz G, Ligon KL, Palescandolo E, Van Hummelen P, Ducar MD, Raza A, Sunkavalli A, MacConaill LE, Stemmer-Rachamimov AO, Louis DN, Hahn WC, Dunn IF, Beroukhim R (2013) Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. Nat Genet 45(3):285–289. https://doi.org/10.1038/ng.2526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Clark VE, Erson-Omay EZ, Serin A, Yin J, Cotney J, Ozduman K, Avşar T, Li J, Murray PB, Henegariu O, Yilmaz S, Günel JM, Carrión-Grant G, Yilmaz B, Grady C, Tanrikulu B, Bakircioğlu M, Kaymakçalan H, Caglayan AO, Sencar L, Ceyhun E, Atik AF, Bayri Y, Bai H, Kolb LE, Hebert RM, Omay SB, Mishra-Gorur K, Choi M, Overton JD, Holland EC, Mane S, State MW, Bilgüvar K, Baehring JM, Gutin PH, Piepmeier JM, Vortmeyer A, Brennan CW, Pamir MN, Kiliç T, Lifton RP, Noonan JP, Yasuno K, Günel M (2013) Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. Science 339(6123):1077–1080. https://doi.org/10.1126/science.1233009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sandberg AA, Stone JF (2008) The genetics and molecular biology of neural tumors. Springer, New York

    Book  Google Scholar 

  7. Jacoby LB, Pulaski K, Rouleau GA, Martuza RL (1990) Clonal analysis of human meningiomas and schwannomas. Cancer Res 50(21):6783–6786

    CAS  PubMed  Google Scholar 

  8. Zhu J, Frosch MP, Busque L, Beggs AH, Dashner K, Gilliland DG, Black PM (1995) Analysis of meningiomas by methylation- and transcription-based clonality assays. Cancer Res 55(17):3865–3872

    CAS  PubMed  Google Scholar 

  9. van den Munckhof P, Christiaans I, Kenter SB, Baas F, Hulsebos TJ (2012) Germline SMARCB1 mutation predisposes to multiple meningiomas and schwannomas with preferential location of cranial meningiomas at the falx cerebri. Neurogenetics 13(1):1–7. https://doi.org/10.1007/s10048-011-0300-y

    Article  PubMed  Google Scholar 

  10. Collins VP, Nordenskjold M, Dumanski JP (1990) Molecular genetics of meningioma. Brain Pathol 1(1):19–24

    Article  Google Scholar 

  11. Simon M, von Deimling A, Larson JJ, Wellenreuther R, Kaskel P, Waha A, Warnick RE, Tew JM, Menon AG (1995) Allelic losses on chromosomes 14, 10, and 1 in atypical and malignant meningiomas: a genetic model of meningioma progression. Cancer Res 55(20):4696

    CAS  PubMed  Google Scholar 

  12. Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR, Zumbo P, Nayir A, Bakkaloglu A, Ozen S, Sanjad S, Nelson-Williams C, Farhi A, Mane S, Lifton RP (2009) Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci USA 106(45):19096–19101. https://doi.org/10.1073/pnas.0910672106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25(14):1754–1760. https://doi.org/10.1093/bioinformatics/btp324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Li B, Dewey CN (2011) RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform 12:323. https://doi.org/10.1186/1471-2105-12-323

    Article  CAS  Google Scholar 

  15. Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P, Franz M, Grouios C, Kazi F, Lopes CT, Maitland A, Mostafavi S, Montojo J, Shao Q, Wright G, Bader GD, Morris Q (2010) The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res 38(suppl_2):W214–W220. https://doi.org/10.1093/nar/gkq537

    Article  Google Scholar 

  16. Chen J, Bardes EE, Aronow BJ, Jegga AG (2009) ToppGene suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res 37(suppl_2):W305–W311. https://doi.org/10.1093/nar/gkp427

    Article  Google Scholar 

  17. Mi H, Muruganujan A, Thomas PD (2013) PANTHER in 2013: modeling the evolution of gene function, and other gene attributes, in the context of phylogenetic trees. Nucleic Acids Res 41(D1):D377–D386. https://doi.org/10.1093/nar/gks1118

    Google Scholar 

  18. Koh YC, Yoo H, Whang GC, Kwon OK, Park HI (2001) Multiple meningiomas of different pathological features: case report. J Clin Neurosci 8(Suppl 1):40–43. https://doi.org/10.1054/jocn.2001.0875

    Article  PubMed  Google Scholar 

  19. Mocker K, Holland H, Ahnert P, Schober R, Bauer M, Kirsten H, Koschny R, Meixensberger J, Krupp W (2011) Multiple meningioma with different grades of malignancy: case report with genetic analysis applying single-nucleotide polymorphism array and classical cytogenetics. Pathol Res Pract 207(1):67–72. https://doi.org/10.1016/j.prp.2010.09.001

    Article  PubMed  Google Scholar 

  20. Tomita T, Kurimoto M, Yamatani K, Nagai S, Kuwayama N, Hirashima Y, Endo S (2003) Multiple meningiomas consisting of fibrous meningioma and anaplastic meningioma. J Clin Neurosci 10(5):622–624. https://doi.org/10.1016/s0967-5868(03)00161-9

    Article  PubMed  Google Scholar 

  21. Yang G, Chen X, Li CG, Zhang DM, Zhang WG, Shi CB, Zhao SG (2013) Multiple meningiomas characterized by benign and malignant tumor entities. CNS Neurosci Ther 19(12):984–986. https://doi.org/10.1111/cns.12179

    Article  CAS  PubMed  Google Scholar 

  22. Yudoyono F, Sidabutar R, Arifin MZ, Faried A (2015) Multiple meningiomas consisting of fibrous meningioma, transitional meningioma, and meningotheliomatous meningioma in one adult patient. Asian J Neurosurg 10(4):348–349. https://doi.org/10.4103/1793-5482.162729

    Article  PubMed  PubMed Central  Google Scholar 

  23. Dewan R, Pemov A, Dutra AS, Pak ED, Edwards NA, Ray-Chaudhury A, Hansen NF, Chandrasekharappa SC, Mullikin JC, Asthagiri AR, Program NCS, Heiss JD, Stewart DR, Germanwala AV (2017) First insight into the somatic mutation burden of neurofibromatosis type 2-associated grade I and grade II meningiomas: a case report comprehensive genomic study of two cranial meningiomas with vastly different clinical presentation. BMC Cancer 17:127. https://doi.org/10.1186/s12885-017-3127-6

    Article  PubMed  PubMed Central  Google Scholar 

  24. Liu Y, Zhang J, Li L, Yin G, Zhang J, Zheng S, Cheung H, Wu N, Lu N, Mao X, Yang L, Zhang J, Zhang L, Seth S, Chen H, Song X, Liu K, Xie Y, Zhou L, Zhao C, Han N, Chen W, Zhang S, Chen L, Cai W, Li L, Shen M, Xu N, Cheng S, Yang H, Lee JJ, Correa A, Fujimoto J, Behrens C, Chow CW, William WN, Heymach JV, Hong WK, Swisher S, Wistuba II, Wang J, Lin D, Liu X, Futreal PA, Gao Y (2016) Genomic heterogeneity of multiple synchronous lung cancer. Nature Commun 7:13200. https://doi.org/10.1038/ncomms13200

    Article  CAS  Google Scholar 

  25. Wheeler SR, Shi C, Holt JA, Vnencak-Jones CL (2016) Mutation profiles of synchronous colorectal cancers from a patient with Lynch syndrome suggest distinct oncogenic pathways. J Gastrointest Oncol 7(3):E64-71. https://doi.org/10.21037/jgo.2016.01.07

    Article  PubMed  Google Scholar 

  26. Akagi K, Kurahashi H, Arita N, Hayakawa T, Monden M, Mori T, Takai S, Nishisho I (1995) Deletion mapping of the long arm of chromosome 22 in human meningiomas. Int J Cancer 60(2):178–182. https://doi.org/10.1002/ijc.2910600208

    Article  CAS  PubMed  Google Scholar 

  27. Chang IB, Cho BM, Moon SM, Park SH, Oh SM, Cho SJ (2010) Loss of heterozygosity at 1p, 7q, 17p, and 22q in meningiomas. J Korean Neurosurg Soci 48(1):14. https://doi.org/10.3340/jkns.2010.48.1.14

    Article  CAS  Google Scholar 

  28. Ruttledge MH, Xie YG, Han FY, Peyrard M, Collins VP, Nordenskjöld M, Dumanski JP (1994) Deletions on chromosome 22 in sporadic meningioma. Genes Chromosom Cancer 10(2):122–130

    Article  CAS  PubMed  Google Scholar 

  29. Seizinger BR, de la Monte S, Atkins L, Gusella JF, Martuza RL (1987) Molecular genetic approach to human meningioma: loss of genes on chromosome 22. Proc Natl Acad Sci USA 84(15):5419–5423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Meese E, Blin N, Zang KD (1987) Loss of heterozygosity and the origin of meningioma. Hum Genet 77(4):349–351

    Article  CAS  PubMed  Google Scholar 

  31. Mihaila D, Gutiérrez JA, Rosenblum ML, Newsham IF, Bögler O, Rempel SA, Consortium NC (2003) Meningiomas: analysis of loss of heterozygosity on chromosome 10 in tumor progression and the delineation of four regions of chromosomal deletion in common with other cancers. Clin Cancer Res 9(12):4435–4442

    CAS  PubMed  Google Scholar 

  32. Chang S-C, Lin J-K, Lin T-C, Liang W-Y (2005) Loss of heterozygosity: an independent prognostic factor of colorectal cancer. World J Gastroenterol 11(6):778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Bale AE (2002) Hedgehog signaling and human disease. Ann Rev Genomics Hum Genet 3:47–65. https://doi.org/10.1146/annurev.genom.3.022502.103031

    Article  CAS  Google Scholar 

  34. Laurendeau I, Ferrer M, Garrido D, D’Haene N, Ciavarelli P, Basso A, Vidaud M, Bieche I, Salmon I, Szijan I (2010) Gene expression profiling of the hedgehog signaling pathway in human meningiomas. Mol Med 16(7–8):262–270. https://doi.org/10.2119/molmed.2010.00005

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Mawrin C, Perry A (2010) Pathological classification and molecular genetics of meningiomas. J Neurooncol. https://doi.org/10.1007/s11060-010-0342-2

    Google Scholar 

  36. Pecina-Slaus N, Kafka A, Lechpammer M (2016) Molecular genetics of intracranial meningiomas with emphasis on canonical Wnt signalling. Cancers 8(7):67. https://doi.org/10.3390/cancers8070067

    Article  PubMed Central  Google Scholar 

  37. Ragel BT, Jensen RL (2010) Aberrant signaling pathways in meningiomas. J Neurooncol 99(3):315–324. https://doi.org/10.1007/s11060-010-0381-8

    Article  CAS  PubMed  Google Scholar 

  38. Wrobel G, Roerig P, Kokocinski F, Neben K, Hahn M, Reifenberger G, Lichter P (2005) Microarray-based gene expression profiling of benign, atypical and anaplastic meningiomas identifies novel genes associated with meningioma progression. Int J Cancer 114(2):249–256. https://doi.org/10.1002/ijc.20733

    Article  CAS  PubMed  Google Scholar 

  39. Choy W, Kim W, Nagasawa D, Stramotas S, Yew A, Gopen Q, Parsa AT, Yang I (2011) The molecular genetics and tumor pathogenesis of meningiomas and the future directions of meningioma treatments. Neurosurg Focus 30(5):E6. https://doi.org/10.3171/2011.2.FOCUS1116

    Article  PubMed  Google Scholar 

  40. Song L, Li ZY, Liu WP, Zhao MR (2015) Crosstalk between Wnt/beta-catenin and Hedgehog/Gli signaling pathways in colon cancer and implications for therapy. Cancer Biol Ther 16(1):1–7. https://doi.org/10.4161/15384047.2014.972215

    Article  PubMed  PubMed Central  Google Scholar 

  41. Taipale J, Beachy PA (2001) The hedgehog and Wnt signalling pathways in cancer. Nature 411

  42. Huard CC, Tremblay CeS, Helsper K, Delisle M-C, Schindler D, L ´evesque G, Carreau M (2012) Fanconi anemia proteins interact with CtBP1 and modulate the expression of the Wnt antagonist Dickkopf-1. Blood. https://doi.org/10.1182/blood-201202-408997

    Google Scholar 

  43. Huard CC, Tremblay CS, Magron A, Levesque G, Carreau M (2014) The Fanconi anemia pathway has a dual function in Dickkopf-1 transcriptional repression. Proc Natl Acad Sci USA 111(6):2152–2157. https://doi.org/10.1073/pnas.1314226111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by Creative-Pioneering Researchers Program through Seoul National University (SNU No. 800-20160282).

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University Hospital, 103 Daehak-ro (Yeongeon-dong), Jongno-gu, Seoul, South Korea

    Tamrin Chowdhury, Yun-Sik Dho, Sojin Kim, Anna Choi, Chul-Kee Park & Ji Yeoun Lee

  2. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea

    Yongjin Yoo & Murim Choi

  3. Department of Neurosurgery, Yeungnam University College of Medicine, Daegu, South Korea

    Youngbeom Seo

  4. Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea

    Sung-Hye Park

  5. Department of Neurosurgery, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea

    Sang Hyung Lee

  6. Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul, South Korea

    Ji Yeoun Lee

Authors
  1. Tamrin Chowdhury
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yongjin Yoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Youngbeom Seo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yun-Sik Dho
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sojin Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anna Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Murim Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sung-Hye Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chul-Kee Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sang Hyung Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ji Yeoun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Sang Hyung Lee or Ji Yeoun Lee.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

This study was approved by the Seoul National University Hospital institutional review board.

Research involving human and animal rights

This article does not contain any studies with animals performed by any of the authors.

Informed consent

The written consent was taken from the patient according to the Institutional Review Board guidelines before tumor removal.

Additional information

Data availability

The datasets analyzed during the current study are available in the NCBI sequence read archive under BioSample accessions SAMN7566682, SAMN7566683, SAMN7566684.

Tamrin Chowdhury and Yongjin Yoo are co-first authors.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (RAR 3085 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chowdhury, T., Yoo, Y., Seo, Y. et al. Genomic analysis of synchronous intracranial meningiomas with different histological grades. J Neurooncol 138, 41–48 (2018). https://doi.org/10.1007/s11060-018-2772-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-018-2772-1

Keywords

Search

Navigation