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Chromosomal imbalances in brain metastases of solid tumors
I Petersen1, A Hidalgo, S Petersen
1Institute of Pathology, Charité - Campus Mitte, Berlin, FRG. iver.petersen@charite.de
Abstract:
Metastases account for approximately 50% of the malignant tumors in the brain. In order to identify structural alterations that are associated with tumor dissemination into the central nervous system we used Comparative Genomic Hybridization (CGH) to investigate 42 brain metastases and 3 primary tumors of 40 patients. The metastases originated from lung cancer (14 cases), melanomas (7), carcinomas of breast (5), colon (5), kidney (5), adrenal gland (1) and thyroid (1). In addition, tumors of initially unknown primaries were assessed in 3 cases. The highest incidence of DNA gains were observed for the chromosomal regions 1q23, 8q24, 17q24-q25, 20q13 (>80% of cases) followed by the gain on 7p12 (77%). DNA losses were slightly less frequent with 4q22, 4q26, 5q21, 9p21 being affected in at least 70% of the cases followed by deletions at 17p12, 4q32q34, 10q21, 10q23-q24 and 18q21-q22 in 67.5% of cases. Two unusual narrow regional peaks were observed for the gain on 17q24-q25 and loss on 17p12. The incidence at individual loci can be viewed at our CGH online tumor database at http:// amba.charite.de/cgh/. The metastases of each tumor type showed a recurrent pattern of changes. In those cases with primary tumor and metastases available, the CGH pattern exhibited a high degree of conformity. In conclusion, our data suggests that specific genetic lesions are associated with tumor dissemination into the nervous system and that CGH analysis may be a useful supplementary tool for classification of metastases with unknown origin.
Insights
Specific genetic changes in brain metastases were identified using Comparative Genomic Hybridization (CGH). These alterations are linked to tumor spread into the central nervous system, aiding in classifying unknown primary tumors.
Area of Science:
- Oncology
- Genetics
- Neuro-oncology
Background:
- Brain metastases represent a significant portion of central nervous system malignancies.
- Understanding the genetic underpinnings of tumor dissemination is crucial for diagnosis and treatment.
Purpose of the Study:
- To identify structural genomic alterations associated with brain metastases using Comparative Genomic Hybridization (CGH).
- To investigate CGH patterns in metastases from various primary tumor types and compare them with primary tumors.
Main Methods:
- Comparative Genomic Hybridization (CGH) was performed on 42 brain metastases and 3 primary tumors from 40 patients.
- Tumor samples included metastases from lung cancer, melanoma, breast, colon, kidney, adrenal gland, and thyroid cancers.
Main Results:
- Frequent DNA gains were observed at chromosomal regions 1q23, 8q24, 17q24-q25, and 20q13 (>80%).
- Common DNA losses occurred at 4q22, 4q26, 5q21, and 9p21 (≥70%).
- CGH patterns showed consistency within tumor types and between primary tumors and their metastases.
Conclusions:
- Specific genetic lesions are associated with the dissemination of tumors to the central nervous system.
- CGH analysis can serve as a valuable supplementary tool for classifying metastases of unknown primary origin.