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Clinical and molecular stratification of disease risk in medulloblastoma

Clinical and molecular stratification of disease risk in medulloblastoma
Clinical and molecular stratification of disease risk in medulloblastoma
The accurate assessment of disease risk among children with medulloblastoma remains a major challenge to the field of paediatric neuro-oncology. In the current study we investigated the capacity of molecular abnormalities to increase the accuracy of disease risk stratification above that afforded by clinical staging alone. 41 primary medulloblastoma tumour samples were analysed for ErbB2 receptor expression using immunohistochemistry, and for aberrations of chromosome 17 and amplification of the MYC oncogene using fluorescence in situ hybridisation. The ErbB2 receptor and deletion of 17p were detected in 80% and 49% of tumours, respectively. 17p loss occurred either in isolation (20%), or in association with gain of 17q (29%), compatible with an isochromosome of 17q. Amplification of MYC was detected in only 2 tumours. Significant prognostic factors included, 'metastatic disease' (P = 0.0006), 'sub-total tumour resection' (P = 0.007), 'high ErbB2 receptor expression' (P = 0.003) and 'isolated 17p loss' (P = 0.003). Combined analysis of clinical and molecular factors enabled greater resolution of disease risk than clinical factors alone, identifying a sub-population of patients with particularly favourable disease outcome. These data support the hypothesis that a combination of clinical and molecular factors may afford a more reliable means of assigning disease risk in patients with medulloblastoma, thereby providing a more accurate basis for targeting therapy in children with this disease.
medulloblastoma, prognosis, ErbB2, MYC, chromosome 17
0007-0920
705-712
Gilbertson, R.
13c238c9-a213-4c22-baac-34378c48b033
Wickramasinghe, C.
1a2d7e51-a64b-4f6a-b924-84f790b9492d
Hernan, R.
d240ddc0-c8d8-40b7-914f-bcda3a189af9
Balaji, V.
545789cb-fe71-4c59-a675-aa882b76abf3
Hunt, D.
0d40b199-1380-40a2-9899-82118c506625
Jones-Wallace, D.
5722b46f-fcad-4460-8b1f-57d758608bb3
Crolla, J.
c5f23751-8de9-4a55-9cc5-ca2fb635769c
Perry, R.
40cdf881-b9da-4bac-a76a-89c6fcf156a5
Lunec, J.
0f31c0e3-da73-4369-bbd2-0a2b5d2fc6f5
Pearson, A.
c0d9b909-dff1-4bed-aecd-83a36225077c
Ellison, D.
cf40fd39-b8e2-4fe7-9cd7-ea4f4cdc3a02
Gilbertson, R.
13c238c9-a213-4c22-baac-34378c48b033
Wickramasinghe, C.
1a2d7e51-a64b-4f6a-b924-84f790b9492d
Hernan, R.
d240ddc0-c8d8-40b7-914f-bcda3a189af9
Balaji, V.
545789cb-fe71-4c59-a675-aa882b76abf3
Hunt, D.
0d40b199-1380-40a2-9899-82118c506625
Jones-Wallace, D.
5722b46f-fcad-4460-8b1f-57d758608bb3
Crolla, J.
c5f23751-8de9-4a55-9cc5-ca2fb635769c
Perry, R.
40cdf881-b9da-4bac-a76a-89c6fcf156a5
Lunec, J.
0f31c0e3-da73-4369-bbd2-0a2b5d2fc6f5
Pearson, A.
c0d9b909-dff1-4bed-aecd-83a36225077c
Ellison, D.
cf40fd39-b8e2-4fe7-9cd7-ea4f4cdc3a02

Gilbertson, R., Wickramasinghe, C., Hernan, R., Balaji, V., Hunt, D., Jones-Wallace, D., Crolla, J., Perry, R., Lunec, J., Pearson, A. and Ellison, D. (2001) Clinical and molecular stratification of disease risk in medulloblastoma. British Journal of Cancer, 85 (5), 705-712. (doi:10.1054/bjoc.2001.1987).

Record type: Article

Abstract

The accurate assessment of disease risk among children with medulloblastoma remains a major challenge to the field of paediatric neuro-oncology. In the current study we investigated the capacity of molecular abnormalities to increase the accuracy of disease risk stratification above that afforded by clinical staging alone. 41 primary medulloblastoma tumour samples were analysed for ErbB2 receptor expression using immunohistochemistry, and for aberrations of chromosome 17 and amplification of the MYC oncogene using fluorescence in situ hybridisation. The ErbB2 receptor and deletion of 17p were detected in 80% and 49% of tumours, respectively. 17p loss occurred either in isolation (20%), or in association with gain of 17q (29%), compatible with an isochromosome of 17q. Amplification of MYC was detected in only 2 tumours. Significant prognostic factors included, 'metastatic disease' (P = 0.0006), 'sub-total tumour resection' (P = 0.007), 'high ErbB2 receptor expression' (P = 0.003) and 'isolated 17p loss' (P = 0.003). Combined analysis of clinical and molecular factors enabled greater resolution of disease risk than clinical factors alone, identifying a sub-population of patients with particularly favourable disease outcome. These data support the hypothesis that a combination of clinical and molecular factors may afford a more reliable means of assigning disease risk in patients with medulloblastoma, thereby providing a more accurate basis for targeting therapy in children with this disease.

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More information

Published date: 2001
Keywords: medulloblastoma, prognosis, ErbB2, MYC, chromosome 17

Identifiers

Local EPrints ID: 24711
URI: http://eprints.soton.ac.uk/id/eprint/24711
ISSN: 0007-0920
PURE UUID: 351dc55c-a9f8-444a-9bb7-d84402f80fa6

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Date deposited: 03 Apr 2006
Last modified: 15 Mar 2024 06:57

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Contributors

Author: R. Gilbertson
Author: C. Wickramasinghe
Author: R. Hernan
Author: V. Balaji
Author: D. Hunt
Author: D. Jones-Wallace
Author: J. Crolla
Author: R. Perry
Author: J. Lunec
Author: A. Pearson
Author: D. Ellison

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