Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Desmoid tumor is a locally aggressive, nonmetastasizing soft tissue tumor. Whether desmoid tumor is a truly neoplastic cellular proliferative process or, alternatively, an unchecked reactive process has been a subject of debate. In order to determine whether desmoid tumor is composed of a clonal cell population as opposed to being a polyclonal reactive process, analysis of patterns of X-chromosome inactivation was performed. Hematoxylin and eosin stained sections of paraffin-embedded, formalin-fixed tissues were microdissected to obtain both lesional and normal control samples, and the genomic DNAs were extracted by proteinase K digestion. Following treatment with methylation sensitive restriction endonuclease (Hha I or Hpa II), the genomic DNAs were amplified by polymerase chain reaction (PCR), using nested primers targeted to a highly polymorphic short tandem repeat (STR) of the human androgen receptor (HUMARA). In eight of 12 cases, PCR amplification of the genomic DNAs was successful, and all eight of the amplified cases were heterozygous in the size of the HUMARA target. The remaining cases could not be studied because of failure to amplify DNA. Following digestion with HhaI or Hpa II, uniform patterns of X-chromosome inactivation were found in all eight desmoid tumors, whereas normal control tissue remained heterozygous. These results confirm a clonal composition of the tumors. The demonstration of clonality in the tumors in all eight informative cases indicates that desmoid tumor is a true neoplastic process, not an unchecked polyclonal reactive process.
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PMID:Desmoid tumor is a clonal cellular proliferation: PCR amplification of HUMARA for analysis of patterns of X-chromosome inactivation. 906 Jun

The fragile histidine triad (FHIT) gene encompasses the common chromosomal fragile site FRA3B. Human papilloma virus (HPV), which is the main aetiological agent in cervical cancers, has been found to be able to integrate its genes into the chromosome 3 fragile site of cultured cells, deleting a piece of DNA which includes the FHIT gene. Eighty-six microdissected archival cervical LLETZ biopsies comprising cases of cervical intraepithelial neoplasia (CIN) 1 (n=27), CIN3 (n=30) and microinvasive carcinoma (n=29) were evaluated for HPV infection and FHIT gene loss of heterozygosity (LOH). FHIT gene LOH was detected by polymerase chain reaction (PCR) using fluorescently labelled intragenic microsatellite markers D3S1300 and D3S4103. PCR products were analysed on a semi-automated DNA sequencer using Fragment Manager(trade mark) software to determine allele loss. The HPV status of the lesions was determined by PCR using generic and type-specific primers in conjunction with restriction endonuclease digestion. The results were analysed using Epi-Info and SPSS-PC statistical analysis software. Haematoxylin and eosin-stained sections from the 86 cases were profiled for six histopathological features, some of which have been previously shown to be associated with microinvasive cancer. FHIT gene LOH was found in 36% of CIN1 cases, 52% of CIN3 cases and 73% of microinvasive cases (p=0.029). HPV 16 DNA was found in 68% of CIN3 cases and 93% of microinvasive cases (p<0.001). The second most prevalent HPV type found was HPV 31, which was present in only four lesions, three of which had FHIT gene LOH. When FHIT gene LOH was evaluated versus HPV 16 and 31 infection using the chi-square test, a statistically significant relationship was found (p=0.014). FHIT gene LOH was found to be independent of the histopathological features evaluated. The finding of a statistically significant relationship between FHIT gene LOH and oncogenic HPV infection suggests a link between the integration of viral DNA and subsequent gene deletion in the progression of cervical cancer. FHIT gene anomalies may prove to be excellent markers of progression in early uterine cervical cancers.
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PMID:Deletion of the FHIT gene in neoplastic and invasive cervical lesions is related to high-risk HPV infection but is independent of histopathological features. 1111 68