[Epigenetic changes in the promoter of the fragile histidine triad (FHIT) gene in human sebocytes under the influence of in vitro culture].

Background: Due to the lack of tumor suppressor function of the fragile histidine triad (FHIT) gene product, sebaceous gland carcinomas can develop.

Objective: The model of the sebocyte cell line SZ95 was used to identify methylated CpG islands at the 5'-end of the FHIT gene and the decrease of gene expression as well as the increase of double-stranded (ds) DNA breaks were examined.

Material And Methods: Methylation, immunofluorescence analysis, promotor sequencing and treatment of SZ95 cells with 5‑azacytidine/trichostatin A (TSA).

Identification of lymphocyte cell-specific protein-tyrosine kinase (LCK) as a driver for invasion and migration of oral cancer by tumor heterogeneity exploitation.

Background: Cancer metastases are the main cause of lethality. The five-year survival rate for patients diagnosed with advanced stage oral cancer is 30%. Hence, the identification of novel therapeutic targets is an urgent need.

Prospero-related homeobox 1 (PROX1) is frequently inactivated by genomic deletions and epigenetic silencing in carcinomas of the bilary system.

Background/aims: Functional deletion of the transcription factor Prospero-related homeobox 1 (PROX1) causes abnormal cellular proliferation via down-regulated expression of the cell cycle inhibitors p27(kip1) and p57(kip2). Hence, we examined whether inactivation of the PROX1 gene can be demonstrated in malignant tumors of the bilary system.

Methods: Seventeen paraffin-embedded specimens of carcinomas of the bilary system were subjected to loss-of-heterozygosity (LOH) and microsatellite instability analyses, methylation-specific polymerase-chain reaction (MSP) and immunohistochemical detection of PROX1 protein in tumor sections.

Forced expression of deltaN-TCF-1B in colon cancer derived cell lines is accompanied by the induction of CEACAM5/6 and mesothelin.

The colon cancer cell lines HT29 and SW480 were transfected with an N-terminal beta-catenin binding site-deficient high mobility group (HMG)-box T-cell factor 1 (deltaN-TCF-1) construct to identify differentially expressed genes. Oligonucleotide HG-U133A microarray expression profiling revealed increased mRNA levels of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 5, 6 and mesothelin in transfectants positive for nuclear deltaN-TCF-1B. Increased amounts of CEACAM5 (CEA) were detectable in membrane-associated compartments, particularly in cholesterol-enriched microdomains.

Genetic testing for germline mutations of the APC gene in patients with apparently sporadic desmoid tumors but a family history of colorectal carcinoma.

Purpose: Desmoid tumors, also known as aggressive fibromatosis, occur with an incidence of 10 to 15 percent in patients affected by familial adenomatous polyposis, an autosomal inherited disease caused by germline mutations in the APC gene. However, sporadic forms with no hereditary background exist. The aim of this study was to find out whether there are APC germline mutations in apparently sporadic desmoid tumor patients without clinical or familial signs of familial adenomatous polyposis but with a family history of colorectal carcinoma in at least one family member.

Frequency and clinical features of visceral malignancy in a consecutive case series of patients with periocular sebaceous gland carcinoma.

Purpose: To report the frequency and clinical features of internal visceral malignancy in an unselected series of patients with sebaceous gland carcinoma (SGC).

Methods: A non-comparative retrospective case series of consecutive patients with a histologically proven diagnosis of periocular sebaceous cell carcinoma treated at the University Eye Hospital, University of Erlangen-Nürnberg between 1981 and 2000.

Results: Twenty-three patients were identified, each with one tumor.

Genetic screening for Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome is clinically characterized by mucocutaneous melanocytic pigmentation, intestinal hamartomatous polyposis and a significantly increased risk of developing cancer. Mutations in the serine/threonine kinase (STK-)11 gene, also designated LKB1, are found in approximately 60% of cases of Peutz-Jeghers syndrome. There is evidence that genetic heterogeneity exists and gene(s) that have not yet been discovered may be responsible for the disease.

Alteration of the fragile histidine triad gene in intrahepatic cholangiocarcinoma.

Background And Aims: Intrahepatic cholangiocarcinoma is the second most common intrahepatic neoplasm, accounting for 10-30% of primary liver cancers. Since little is known about the development of this cancer, we searched for alterations to the fragile histidine triad (FHIT) gene, a putative tumour suppressor gene on chromosome 3p14.2.

Loss of fragile histidine triad (FHIT) expression and microsatellite instability in periocular sebaceous gland carcinoma in patients with Muir-Torre syndrome.

Purpose: To report fragile histidine triad expression and microsatellite instability in periocular sebaceous gland carcinoma.

Design: Interventional case series.

Methods: Biopsy specimens of periocular sebaceous gland carcinoma obtained from six patients (mean age, 60 +/- 17 years; range, 38 to 83 years, 5 male, 1 female) with Muir-Torre syndrome and histopathologically proven sebaceous gland carcinoma were studied immunohistochemically for the presence of fragile histidine triad protein.