Biomedical subjects

Philipp U Heitz

Publications and source records attributed to Philipp U Heitz.

22 records · Page 2Linked to original sources

PubMed2002

Loss of heterozygosity at chromosome 6q23-25 correlates with clinical and histologic parameters in salivary gland adenoid cystic carcinoma.

The prognosis of salivary gland adenoid cystic carcinoma (ACC) depends on the clinical stage, the location of the primary tumor, and the histologic growth pattern. ACCs with a cribriform growth pattern have a better prognosis than those with a solid growth pattern; however, clear-cut grading criteria have not yet been established, and therefore prognostic indicators on a molecular level are of special interest. In order to analyze tumor tissue with different growth patterns, cribriform and solid tumor areas of 25 patients were microdissected and separately analyzed for loss of heterozygosity (LOH) at nine polymorphic microsatellite markers located between 6q14 and 6q27. LOH was detected in 19/25 (76%) patients and LOH rates were highest at markers D6S441, D6S310, D6S311 and UTRN, which are located at 6q23-25. Combined analysis of LOH at these four markers shows that in primary tumor subtype foci with cribriform growth pattern LOH is associated with high TNM stages (P<0.01), high T stages (P=0.01), positive lymph node status (P=0.03), an unfavorable disease course (P=0.02), and the presence of >10% solid growth pattern (P=0.05). In contrast, in primary tumor subtype foci with solid growth pattern, no significant differences in LOH rates were found in patients from prognostically and histologically favorable versus unfavorable patient groups. The frequent occurrence of LOH at 6q23-25 and the correlation of LOH rates with prognostic parameters indicate that a prognostically important tumor suppressor gene is located in this chromosomal area.

Adult↗

PubMed2002

High frequency of t(14;18)-translocation breakpoints outside of major breakpoint and minor cluster regions in follicular lymphomas: improved polymerase chain reaction protocols for their detection.

The detection of t(14;18) translocations is widely used for the diagnosis and monitoring of follicular lymphomas displaying a high prevalence for this aberration. Cytogenetics, Southern blotting, and polymerase chain reaction (PCR) are commonly used techniques. It is generally believed that the vast majority of the breakpoints occurs on chromosome 18 in the major breakpoint region (mbr) and the minor cluster region (mcr). Yet, by improving long-distance PCR protocols we identified half of the breakpoints outside of these clusters. Our study included biopsies from 59 patients with follicular lymphoma. Seventy-one percent carried translocations detectable with our long-distance PCR protocol. The novel primer sets were derived from the hitherto uncharacterized 25-kb-long stretch between mbr and mcr that we have sequenced for this purpose. Sequence analysis of the novel breakpoints reveals a wide distribution between mbr and mcr displaying some clustering 16 kb downstream from the BCL2 gene. By including a primer for this intermediate cluster region in standard PCRs we could also improve the detection of t(14;18) translocations in formalin-fixed and paraffin-embedded biopsies. Our new PCRs are highly sensitive, easy to perform, and thus well suited for routine analysis of t(14;18) translocations for the primary diagnosis of follicular lymphoma and surveillance of minimal residual disease.

Chromosomes, Human, Pair 14↗

PubMedDate not supplied

CGH analysis shows genetic similarities and differences in atypical fibroxanthoma and undifferentiated high grade pleomorphic sarcoma.

BACKGROUND: Atypical fibroxanthoma (AFX) and undifferentiated high grade pleomorphic sarcoma (UpS) are histologically very similar, if not identical. However, they differ significantly in clinical outcome. MATERIALS AND METHODS: We used comparative genomic hybridization (CGH) to screen 24 AFX and 12 UpS for genomic alterations. RESULTS: DNA copy number changes were observed in 20/24 AFX and in all UpS. The most frequent alterations occurring with comparable frequency in both tumors were deletions on chromosomes 9p and 13q. We also detected statistically significant differences of genetic alterations between the two tumors concerning deletions on 1q, 3p, 5q, 11p, 11q, gains on 7q, 12q and high level gains on 5p and 11q. CONCLUSION: Despite their very similar histology, AFX and UpS show clear differences in their genetic alterations. This might contribute to the different biological behavior of the two tumors. On the other hand the similarities in genetic alterations on chromosomes 9p and 13q might suggest a common pathogenetic pathway.

Adult↗

PubMedDate not supplied

Absence of BRAF gene mutations differentiates spitz nevi from malignant melanoma.

BACKGROUND: Distinction of Spitz nevus from malignant melanoma is sometimes difficult on the basis of conventional histology. A high rate of BRAF gene mutations in malignant melanomas (66%) and nevi (82%) has recently been reported. MATERIALS AND METHODS: We screened a series of 20 Spitz nevi for BRAF mutations in exons 11 and 15 by denaturing gradient gel electrophoresis (DGGE). RESULTS: BRAF mutations could not be identified in Spitz nevi. CONCLUSION: Our results show that mutations within the BRAF gene are useful markers for the differential diagnosis between Spitz nevus and malignant melanoma.

Adolescent↗