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Kerstin Heselmeyer-Haddad

Staff Scientist 

Phone: 301-451-4921 (office)
301-402-2008 (lab)
301-402-1204 (FAX)
e-mail: heselmek@mail.nih.gov

 


Bibliography

Curriculum Vitae
Interphase cytogenetics with tumor and tumor-stage specific probes detects pivotal chromosomal aberrations in cancer screening samples leading to early and refined diagnosis.

We used Comparative Genomic Hybridization (CGH) to screen for chromosomal aberrations in different tumor types and stages and found that the precancerous and cancerous lesions we investigated showed patterns of chromosomal aberrations which were very specific for the tumor type and stage. In cervical carcinogenesis we detected a 3q gain in 1 out of 13 severe dysplasias/CIS, in 9 out of 10 stage I carcinomas and in 23 out of 30 advanced stage carcinomas of the uterine cervix, indicating that the gain of 3q occurs at the transition to invasive disease. Small breast carcinomas (<10 mm) exhibited a 4q gain in 90% of the cases and frequent gains of 8q, 1q, 5q, 6q and 12q and losses of 16q and 22 while benign fibroadenomas did not show any aberrations. These results strongly suggest that specific aberrations emerge at certain transition points of the lesion and that the identification of these pivotal changes in patient material can lead to earlier and more refined diagnosis and treatment. We identified candidate genes in the regions of interest and screened BAC libraries to generate potent probes for interphase cytogenetics. With the help of these probes or probe panels cells in cancer screening samples like e. g. cervical smears and thinpreps or breast fine-needle aspirates and imprints can be genetically characterized and distinguished. We successfully hybridized cervical thinpreps with a 3q specific probe and breast imprints with different centromere and loci specific probes. Just now we are working on larger materials to investigate the clinical significance of the probes/probe panels we found. Another exciting possibility for the application of these markers is the use of interphase cytogenetics on peripheral blood samples enriched for circulating epithelial cells by ferrofluid coated with antibodies against epithelial markers. Using FISH we detected chromosomal aberrations in cells isolated from patients with organ-confined breast cancer. Interphase cells from the surgically removed primary tumor showed the same aberrations which strongly suggests that the tumor cells detected in the peripheral blood are derived from the primary tumor. This approach could potentially be used as a cancer screening tool in hereditary or environmental risk groups and as a monitor device of patient treatment.


 

Tel: 301 402-2008 Fax: 301 402-1204
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