Определение молекулярно-генетических подгрупп медуллобластомы на основании анализа уровня экспрессии генов

Статья в Elpub

Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2017; 16: 85-89

Определение молекулярно-генетических подгрупп медуллобластомы на основании анализа уровня экспрессии генов

Друй А.Е. , Ясько Л.А. , Коновалов Д.М. , Эктова А.П. , Валиахметова Э.Ф. , Ольшанская Ю. В., Масчан А.А. , Новичкова Г.А. , Папуша Л.И.

https://doi.org/10.24287/1726-1708-2017-16-4-85-89

Аннотация

В основе клинической гетерогенности медуллобластом лежат различия, выявляемые на молекулярном уровне, в виде неодинакового профиля экспрессии генов, метилирования ДНК и мутационного спектра. Выявление данных различий послужило основанием для создания в 2016 году новой классификации опухолей центральной нервной системы, в которой предусмотрено разделение медуллобластом на молекулярно-генетические подгруппы. Принадлежность медуллобластомы к определенной молекулярно-генетической подгруппе определяет исход заболевания, ответ на проводимую терапию, вероятность развития рецидива и прогноз. В настоящей работе представлены результаты использования технологии NanoString для определения молекулярно-генетической подгруппы медуллобластом на 65 гистологических образцах.

Список литературы

1. Coluccia D., Figuereido C., Isik S., Smith C., Rutka J.T. Medulloblastoma: Tumor Biology and Relevance to Treatment and Prognosis Paradigm. Curr Neurol Neurosci Rep 2016; 16 (5): 43-54.

2. Taylor M.D., Northcott P.A., Korshunov A., Remke M., Cho Y.J., Clifford S.C., et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 2012; 123 (4): 465-72.

3. Louis D.N., Perry A., Reifenberger G., von Deimling A., Figarella-Branger D., Cavenee W.K., et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016; 131 (6): 803-20.

4. Northcott P.A., Korshunov A., Pfister S.M., Taylor M.D. The clinical implications of medulloblastoma subgroups. Nat Rev Neurol 2012; 8 (6): 340-51.

5. Pietsch T., Schmidt R., Remke M., Korshunov A., Hovestadt V., Jones D.T., et al. Prognostic significance of clinical, histopathological, and molecular characteristics of medulloblastomas in the prospective HIT2000 multicenter clinical trial cohort. Acta Neuropathol 2014; 128 (1): 137-49.

6. Northcott P.A., Korshunov A., Witt H., Hielscher T., Eberhart C.G., Mack S., et al. Medulloblastoma comprises four distinct molecular variants. J Clin Oncol 2011; 29 (11): 1408-14.

7. Hovestadt V., Remke M., Kool M., Pietsch T., Northcott P.A., Fischer R., et al. Robust molecular subgrouping and copy-number profiling of medulloblastoma from small amounts of archival tumour material using high-density DNA methylation arrays. Acta Neuropathol 2013; 125 (6): 913-16.

8. Northcott P.A., Shih D.J., Remke M., Cho Y.J., Kool M., Hawkins C., et al. Rapid, reliable, and reproducible molecular sub-grouping of clinical medulloblastoma samples. Acta Neuropathol 2012; 123 (4): 615-26.

9. Geiss G.K., Bumgarner R.E., Birditt B., Dahl T., Dowidar N., Dunaway D.L., et al. Direct multiplexed measurement of gene expression with color-coded probe pairs. Nature Biotechnology 2008; 26: 317-25.

10. Gajjar A., Bowers D.C., Karajannis M.A., Leary S., Witt H., Gottardo N.G. Pediatric Brain Tumors: Innovative Genomic Information Is Transforming the Diagnostic and Clinical Landscape. J Clin Oncol 2015; 33 (27): 2986-98.

11. Shih D.J., Northcott P.A., Remke M., Korshunov A., Ramaswamy V., Kool M., et al. Cytogenetic prognostication within medulloblastoma subgroups. J Clin Oncol 2014; 32 (9): 886-96.

12. Pfister S., Remke M., Benner A., Mendrzyk F., Toedt G., Felsberg J., et al. Outcome prediction in pediatric medulloblastoma based on DNA copy-number aberrations of chromosomes 6q and 17q and the MYC and MYCN loci. J Clin Oncol 2009; 27 (10): 1627-36.

13. ЦаурГ.А., ДруйА.Е., ПоповА.М., СеменихинаЕ.Р., РигерТ.О., ИвановаА.С. идр. Возможность использования микроструйных биочипов для оценки качества и количества РНК у пациентов с онкологическими и онкогематологическими заболеваниями. Вест. уральской мед. академич. науки, 2011; 4: 107-11.

14. LiuM.C., PitcherB.N., MardisE.R., DaviesS.R., FriedmanP.N., SniderJ.E., etal. PAM50 gene signatures and breast cancer prognosis with adjuvant anthracycline- and taxane-based chemotherapy: correlative analysis of C9741 (Alliance). NPJ Breast Cancer 2016; 2: 15023.

Pediatric Hematology/Oncology and Immunopathology. 2017; 16: 85-89

Identification of medulloblastoma molecular subgroups by gene expression profiling

Druy A. E., Yasko L. A., Konovalov D. M., Ektova A. P., Valiakhmetova E. F., Olshanskaya Y. V., Maschan A. A., Novichkova G. A., Papusha L. I.

https://doi.org/10.24287/1726-1708-2017-16-4-85-89

Abstract

Clinical heterogeneity of medulloblastoma is based on differences in the molecular landscape of the tumor, which include gene expression and DNA methylation profiles and mutational spectrum. WHO classification of CNS malignancies developed in 2016 implies segregation of medulloblastoma entity into 4 distinct molecular subgroups: WNT, SHH, group 3 and group 4. This division defines clinical presentation, response to therapy, risk of tumor recurrence and presents a basis for individualized and risk-adapted treatment conduction. Molecular genetic techniques for medulloblastoma subgrouping are based either on gene expression profiling or investigation of whole-genome DNA methylation. Method used in clinical practice should be reliable, fast, undemanding for preanalytic procedures and robust. For these reasons gene expression analysis by NanoString technology can be designated. In the current study we present the first Russian experience in the molecular classification of medulloblastoma based on gene expression profiling by Nanostring technique. The retrospective analysis of 65 pathologically verified medulloblastoma samples was performed. Among these cases WNT subgroup was revealed in 8, SHH – in 15, group 3 – in 16 and group 4 in 26 patients. The subgroup distribution as well as clinical significance of each tumor type corresponded to the literature data. Notable, that NanoString technology allowed achieving reliable data on gene expression from complicated material – formalin-fixed paraffin embedded tissue.

References

1. Coluccia D., Figuereido C., Isik S., Smith C., Rutka J.T. Medulloblastoma: Tumor Biology and Relevance to Treatment and Prognosis Paradigm. Curr Neurol Neurosci Rep 2016; 16 (5): 43-54.

2. Taylor M.D., Northcott P.A., Korshunov A., Remke M., Cho Y.J., Clifford S.C., et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 2012; 123 (4): 465-72.

4. Northcott P.A., Korshunov A., Pfister S.M., Taylor M.D. The clinical implications of medulloblastoma subgroups. Nat Rev Neurol 2012; 8 (6): 340-51.

6. Northcott P.A., Korshunov A., Witt H., Hielscher T., Eberhart C.G., Mack S., et al. Medulloblastoma comprises four distinct molecular variants. J Clin Oncol 2011; 29 (11): 1408-14.

11. Shih D.J., Northcott P.A., Remke M., Korshunov A., Ramaswamy V., Kool M., et al. Cytogenetic prognostication within medulloblastoma subgroups. J Clin Oncol 2014; 32 (9): 886-96.

13. TsaurG.A., DruiA.E., PopovA.M., SemenikhinaE.R., RigerT.O., IvanovaA.S. idr. Vozmozhnost' ispol'zovaniya mikrostruinykh biochipov dlya otsenki kachestva i kolichestva RNK u patsientov s onkologicheskimi i onkogematologicheskimi zabolevaniyami. Vest. ural'skoi med. akademich. nauki, 2011; 4: 107-11.