Epigenetic silencing contributes to frequent loss of the fragile histidine triad tumour suppressor in basal cell carcinomas.

Background: Extensive exposure to ultraviolet radiation is associated with genetic alterations in basal cell carcinomas (BCCs), which represent some 75% of skin cancers.

Objectives: As recent data suggested the fragile histidine triad (FHIT) gene product to participate in DNA damage responses we wished to address whether functional deletion of this tumour suppressor participates in the development of BCC. Our study focused on epigenetic inactivation of the FHIT gene.

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.