Global gene expression in neuroendocrine tumors from patients with the MEN1 syndrome

BACKGROUND: Multiple Endocrine Neoplasia type 1 (MEN1, OMIM 131100) is an autosomal dominant disorder characterized by endocrine tumors of the parathyroids, pancreatic islets and pituitary. The disease is caused by the functional loss of the tumor suppressor protein menin, coded by the MEN1 gene. The protein sequence has no significant homology to known consensus motifs. In vitro studies have shown menin binding to JunD, Pem, Smad3, NF-kappaB, nm23H1, and RPA2 proteins. However, none of these binding studies have led to a convincing theory of how loss-of-menin leads to neoplasia. RESULTS: Global gene expression studies on eight neuroendocrine tumors from MEN1 patients and 4 normal islet controls was performed utilizing Affymetrix U95Av2 chips. Overall hierarchical clustering placed all tumors in one group separate from the group of normal islets. Within the group of tumors, those of the same type were mostly clustered together. The clustering analysis also revealed 19 apoptosis-related genes that were under-expressed in the group of tumors. There were 193 genes that were increased/decreased by at least 2-fold in the tumors relative to the normal islets and that had a t-test significance value of p < = 0.005. Forty-five of these genes were increased and 148 were decreased in the tumors relative to the controls. One hundred and four of the genes could be classified as being involved in cell growth, cell death, or signal transduction. The results from 11 genes were selected for validation by quantitative RT-PCR. The average correlation coefficient was 0.655 (range 0.235–0.964). CONCLUSION: This is the first analysis of global gene expression in MEN1-associated neuroendocrine tumors. Many genes were identified which were differentially expressed in neuroendocrine tumors arising in patients with the MEN1 syndrome, as compared with normal human islet cells. The expression of a group of apoptosis-related genes was significantly suppressed, suggesting that these genes may play crucial roles in tumorigenesis in this syndrome. We identified a number of genes which are attractive candidates for further investigation into the mechanisms by which menin loss causes tumors in pancreatic islets. Of particular interest are: FGF9 which may stimulate the growth of prostate cancer, brain cancer and endometrium; and IER3 (IEX-1), PHLDA2 (TSS3), IAPP (amylin), and SST, all of which may play roles in apoptosis

Clinical Study Utility of Surgeon-Performed Ultrasound Assessment of the Lateral Neck for Metastatic Papillary Thyroid Cancer

Ultrasound is the recommended staging modality for papillary thyroid cancer. Surgeons proficient in US assessment of the neck and experienced in the management of papillary thyroid cancer (PTC) appear uniquely qualified to assess the lateral cervical lymph nodes for metastatic disease. Of 310 patients treated for PTC between 2000 and 2008, 109 underwent surgeon-performed ultrasound (SUS) of the lateral neck preoperatively. Fine needle aspiration was performed on suspicious lateral lymph nodes. SUS findings were compared with FNA cytology and results of postoperative imaging studies. The sensitivity and negative predictive value of SUS were 88% and 97%, respectively. Four patients were found to have missed metastatic disease within 6 months. No patient underwent a nontherapeutic neck dissection. SUS combined with US-guided FNA of suspicious lymph nodes can accurately stage PTC to reliably direct surgical management

Isolation of YAC Clones From the Pericentromeric Region of Chromosome 10 and Development of New Genetic Markers Linked to the Multiple Endocrine Neoplasia Type 2A Gene

Genetic linkage mapping and contig assembly using yeast artificial chromosome (YAC) technology form the basis of our strategy to clone and define the genomic structure of the pericentromeric region of chromosome 10 containing the multiple endocrine neoplasia type 2A gene. Thus far YAC walks have been initiated from five chromosome 10 pericentromeric loci including RBP3, D10S94, RET, D10Z1, and FNRB. Long range pulsed-field gel electrophoresis maps are constructed from the YACs isolated to define clone overlaps and to identify putative CpG islands. Bidirectional YAC walks are continued by rescreening the YAC library with sequence-tagged site assays developed from endclones. Several new restriction fragment length polymorphisms and simple sequence repeat polymorphism markers have been identified from the YAC clones. In particular, two highly informative (CA)n dinucleotide repeat markers, sTCL-1 from proximal chromosome 10p (16 alleles, PIC = 0.68) and sJRH-1 from the RBP3 locus (18 alleles. PIC = 0.88), provide useful reagents for a polymerase chain reaction-based predictive genetic test that can be performed rapidly from small amounts of DNA

Academic Appointment and the Process of Promotion and Tenure

A critical component of a successful academic career is the understanding of institutional criteria and guidelines for academic appointment, promotion, and tenure. It is important to point out that these criteria and guidelines may vary from institution to institution; however, they are uniform for all clinical faculty within a single institution and do not differ from department to department. The purpose of this article is to provide the aspiring academic colon and rectal surgeon with a basic understanding of academic faculty appointments, promotion, and tenure