The Genetics Concerning Endocrine Neoplasia - Essay Example

Latest Advances in Genetics Concerning Endocrine Neoplasia Endocrine neoplasia, which is also known as either MEN1, or multiple endocrine neoplasia type 1, or MEN2, is a rare genetic disorder characterized by the growth of tumors in the endocrine glands. The specific anatomical structures commonly affected include the pancreas, parathyroid and the pituitary for MEN1 (“Multiple endocrine neoplasia (MEN) I,” 2010), the adrenal and thyroid for MEN2 (“Multiple endocrine neoplasia (MEN) II,” 2010), and even the duodenum (“Multiple Endocrine Neoplasia Type 1,” 2010). While MEN1 is caused by a problem in the gene that encodes for the protein menin (“Multiple endocrine neoplasia (MEN) I,” 2010), the cause of MEN2 is a problem with the gene RET. Growth of benign and malignant tumors is the most likely consequence of such genetic defects. However, current research focuses on MEN1, which is the more common of the two types of endocrine neoplasia. Experimental studies also focus on other disorders that usually accompany the tumors. One of these is hyperparathyroidism (HPT), which is caused by the overactivity of all four parathyroid glands. HPT causes a series of physiological changes in the blood leading to kidney stones or kidney damage (“Multiple Endocrine Neoplasia Type I,” 2010). Another accompanying disorder is Zollinger-Ellison Syndrome (ZES), which is caused by the growth of multiple tumors in the pancreas or duodenum (Norton et al., 2009). Lastly, lipoma, or lipomatous tumors, may appear in 30% of MEN1 patients. (Dreijerink et al., 2009) Experiment Number 1: Prospective Study of Surgery for Primary Hyperparathyroidism (HPT) in Multiple Endocrine Neoplasia-type 1 (MEN1), and Zollinger-Ellison syndrome (ZES): Long-term Outcome of a More Virulent form of HPT (Norton et al., 2009) Purpose. The most common symptom of MEN1 is hyperparathyroidism (HPT) and it often occurs together with Zollinger-Ellison syndrome (ZES) in the same patient. The problem is that surgery to remove the multiple pancreatic tumors that cause ZES can seldom cure the patient (Norton et al., 2009), thus scientists and doctors need to find a way to remove these tumors in such a way that it will result into a cure. Moreover, partial or complete removal of the parathyroid glands affected with HPT do not seem to produce a cure either as persistent and recurrent HPT reoccurs even after surgical removal of the glands (Norton et al., 2009). The study sought answers to these questions. Hypotheses. HPT commonly occurs with MEN1 with or without ZES, but ZES always occurs in those with HPT. Now, considering that ZES commonly occurs in conjunction with HPT, scientists hypothesize that removal of the HPT-affected parathyroid glands will cure both HPT and ZES. Moreover, since the traditional operation to treat HPT requires the removal of 3 ½ or all 4 parathyroid glands and it does not seem to keep HPT from recurring, then there must be an exact number of parathyroid glands to be removed in order to effect a better cure with no relapses. (Norton et al., 2009) Experimental Design. In 1970, after having diagnosed all 84 patients with HPT using biochemical methods and serum tests, ZES using acid secretory tests, and MEN1 using personal and family history, the patients were then subjected to surgery for primary hyperparathyroidism and the results were followed up within 3 to 6 months after surgery and every year thereafter for 35 years. The parathyroidectomy performed on the patients were done either partially or completely in that some had less than 3 glands removed, some from 3 to 3 ½, and for the rest, all 4 glands were removed. In 2005, the patients were reassessed for any relapses of HPT or whether their ZES was cured or not. (Norton et al., 2009) Results. Upon reassessment of the patients’ medical condition in 2005, it was found out that in patients with less than 3 parathyroid glands removed 3% developed hypoparathyroidism, 86% had a relapse of HPT and 92% developed hypercalcemia, since the parathyroid glands are the organs responsible for the regulation of calcium. For patients with 3 to 3 ½ parathyroid glands removed, 10% of them experienced hypoparathyroidism, 36% still had HPT and 57% hypercalcemia. Lastly, for those who underwent the removal of all 4 or even more parathyroid glands, 22% had hypoparathyroidism and 55% HPT, with no mention of hypercalcemia. It is also interesting to note that 20% of the patients had no more ZES. (Norton et al., 2009) Conclusion. From the results, Norton and his colleagues have concluded that partial parathyroidectomy, which means the removal of 3 to 3 ½ glands, was dangerous and impractical sometime after the operation due to a high incidence of all three disorders: hypoparathyroidism, HPT and hypercalcemia. Nevertheless, the four-gland removal is also not recommended due to a high incidence of HPT, and that the removal of less than 3 glands also does not prove to be as helpful. The researchers admit that the best surgical procedure remains as the removal of 3 ½ glands because the incidence of the three ensuing disorders somehow fall below or slightly above 50%. Unfortunately, there is no ideal surgical procedure for patients with MEN1/HPT/ZES. (Norton et al., 2009) Experiment Number 2: The Multiple Endocrine Neoplasia Type1 (MEN1) Tumor Suppresor Regulates Peroxisome Proliferator-Activated Receptor y-Dependent Adipocyte Differentiation (Dreijerink et al., 2009) Purpose. One complication brought about by MEN1 is the growth of lipomatous tumors or lipoma. Nevertheless, the mechanism of lipomatous tumor formation in MEN1 patients is unknown. However, menin, which is the product of the MEN1 tumor suppressor gene, is believed to be involved in a series of biochemical processes that eventually lead to the activation of a certain portion of the receptor PPARy, which usually occurs in conjunction with lipomas. PPARy is also considered a primary regulator in the differentiation of adipocytes, which are directly linked to lipomas (Dreijerink et al., 2009). There is therefore the need to ascertain whether menin actually triggers lipomatous tumor formation, for if it does then this is one big step towards suppressing the growth of lipomas. Hypothesis. The group of scientists under Dreijerink hypothesize that menin indirectly causes the formation of lipomas by participating in the activation of PPARy. (Dreijerink et al., 2009) Experimental Design. The experiment involved the investigation of four samples of adipose tissue and eight samples of lipomas from the tissue bank and after subjecting the samples to various chemicals, RNA was isolated from them using the RNeasy kit. The process employed on the adipose tissue and lipoma samples was known as reverse transcription analysis. Levels of mRNA in all the genes involved in the study, particularly the PPARy target genes that code for the fatty acid binding protein FABP4, were then measured. (Dreijerink et al., 2009) Results. Based on the results of the reverse transcription analysis, mRNA levels of the FABP4 were greatly reduced in lipoma tissue samples with MEN1 genes. Moreover, through further tests, it was ascertained that PPARy is indeed regulated by menin, and that menin in fact coactivates PPARy. (Dreijerink et al., 2009) Conclusion. The findings somehow establish the fact that indeed menin is linked with PPARy and in fact coactivates it and directs its actions towards the formation of adipocytes. The fact that FABP4 is greatly reduced in lipoma tissue samples with MEN1 suggests that menin triggers the loss of the normal adipocyte-forming function of PPARy and therefore results in the formation of lipomas. The hypothesis was therefore proven to be true and the results of the study further explained the processes behind the theory. References Dreijerink KMA, Varier RA, Van Beekum O, Jeninga EH, Hoppener JWM, Lips CJM, Kummer JA, Kalkhoven E, Timmers HTM. 2009. The Multiple Endocrine Neoplasia Type 1 (MEN1) Tumor Suppressor Regulates Peroxisome Proliferator-Activated Receptor y-Dependent Adipocyte Differentiation. American Society for Microbiology [Internet]. [cited 2010 Nov 8]; 29:18. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2738285/ “Multiple endocrine neoplasia (MEN) I.” Article. 2010. Medline Plus: Trusted Health Information for You [Internet]. [cited 2010 Nov 6]. Available from: http://www.nlm.nih.gov/medlineplus/ency/article/000398.htm “Multiple endocrine neoplasia (MEN) II.” Article. 2010. Medline Plus: Trusted Health Information for You [Internet]. [cited 2010 Nov 6]. Available from: http://www.nlm.nih.gov/medlineplus/ency/article/000399.htm “Multiple Endocrine Neoplasia Type 1.” Information on Endocrine and Metabolic Diseases. 2010. National Endocrine and Metabolic Diseases Information Service [Internet]. [cited 2010 Nov 7]. Available from: http://endocrine.niddk.nih.gov/pubs/men1/men1.htm Norton JA, Venzon DJ, Berna MJ, Alexander HR, Frake DL, Libutti SK, Marx SJ, Gibril F, Jensen RT. 2009. GeneNotes: a novel information management software for biologists. BMC Bioinformatics [Internet]. [cited 2010 Nov 6]; 247:3. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717476/ Read More