Biomedical subjects

Louis J Vitone

Publications and source records attributed to Louis J Vitone.

3 recordsLinked to original sources

PubMed2006

The inherited genetics of pancreatic cancer and prospects for secondary screening.

It is estimated that pancreatic cancer has a familial component in approximately 5-10% of cases. Some of these cases are part of a defined cancer syndrome with a known gene mutation but in the remaining the causative gene remains unknown. In recent years, a better understanding of the molecular events that occur in the progression model of pancreatic cancer has lead to the development of secondary screening programmes with the aim of identifying early precursor lesions or pre-invasive cancer at a stage amenable to curative resection. High-risk groups who have an inherited predisposition for pancreatic cancer form the ideal group to study in developing a robust screening programme. Multimodality screening using computed tomography and endoluminal ultrasound in combination with molecular analysis of pancreatic juice are proving promising as diagnostics tools or at least serving as predictors of risk over a defined period.

Biomarkers, Tumor↗

PubMed2006

Trypsinogen mutations in pancreatic disorders.

There are multiple PRSS1 mutations described in hereditary pancreatitis but only a minority of these are clinically relevant. The two most frequent point mutations are in exon 2 (N29I) and exon3 (R122H), found in diverse racial populations. Both mutations result in early onset pancreatitis but the mechanism underlying this phenotype is unclear. The frequency of these mutations in such diverse populations suggests they have spontaneously occurred many times. The origin of the major mutations may be explained by gene conversions, accounting for multiple founders. The implications are discussed in terms of mechanism of action of the mutations and clinical presentation.

Gene Conversion↗

PubMed2006

Evaluation of the 4q32-34 locus in European familial pancreatic cancer.

BACKGROUND: Familial pancreatic cancer (FPC) describes a group of families where the inheritance of pancreatic cancer is consistent with an autosomal-dominant mode of inheritance. The 4q32-34 region has been previously identified as a potential locus for FPC in a large American family. METHODS: The region was allelotyped in 231 individuals from 77 European families using nine microsatellite markers, and haplotyping was possible in 191 individuals from 41 families. Families were selected based on at least two affected first-degree relatives with no other cancer syndromes. RESULTS: Linkage to most of the locus was excluded based on LOD scores less than -2.0. Eight families were excluded from linkage to 4q32-34 based on haplotypes not segregating with the disease compared with a predicted six to seven families. Two groups of families were identified, which seem to share common alleles within the minimal disease-associated region of 4q32-34, one group with an apparently earlier age of cancer death than the other pancreatic cancer families. Four genes were identified with potential tumor suppressor roles within the locus in regions that could not be excluded based on the LOD score. These were HMGB2, PPID, MORF4, and SPOCK3. DNA sequence analysis of exons of these genes in affected individuals and in pancreatic cancer cell lines did not reveal any mutations. CONCLUSION: This locus is unlikely to harbor a FPC gene in the majority of our European families.

Adenocarcinoma↗