Multiple endocrine neoplasia（MEN）is not as well recognized in Asian countries, including Japan, as in Western countries. Clinical features of MEN and management conditions have yet to be clarified in Japan. Thus, we established a MEN study group, designated the “MEN Consortium of Japan”, in 2008. Its missions are : 1）to clarify the current status of clinical management of MEN, 2）promote basic research, 3）improve the diagnosis and treatment of MEN, 4）promote public relations to increase awareness of MEN, 5）support and collaborate with patient advocacy groups, and so on. Clinical and genetic information on more than 1,000 patients were collected and analyzed. The database established by the MEN Consortium of Japan is the first such database for Asian patients, and is one of the most extensive databases for MEN worldwide. This is anticipated to promote clarification of the current status of MEN in Japan and improve future clinical management.

View full abstract

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited disease characterized by parathyroid hyperplasia, pancreatico-gastroduodenal neuroendocrine tumor (NET), pituitary adenoma, adrenal hyperplasia and thymic NET. The causative gene for MEN1 is MEN1 tumor suppressor gene. Multiple endocrine neoplasia type 2 (MEN2) is also an autosomal dominantly inherited disease characterized by medullary thyroid carcinoma (MTC), adrenal pheochromocytoma and parathyroid hyperplasia. The causative gene for MEN2 is RET oncogene. Prognosis of MEN patients is mainly relied on the presence or absence of progressive/metastatic pancreatic NET or MTC. The effective treatment for these tumors had not been well established. In this paper, we described current situation of genetic diagnosis and new promising drug therapy, everolimus, sunitinib and vandetanib for patients with multiple endocrine neoplasia (MEN) in Japan.

View full abstract

Creation of clinical practice guideline of multiple endocrine neolasiagland (MEN) in our country was the first target of the MEN consortium established in 2008. From 2009, the Ministry of Health, Labour and Welfare Grant-in-Aid-for-Scientific-Research (Intractable Disease Research Program)“ creation of clinical guideline of MEN 1 type and 2 types” research group in which Dr. Sakurai is a research representative was inaugurated. Moreover, the MEN consortium has obtained support also from a Japanese Society of Thyroid Surgery, the Japan Association of Endocrine Surgeons and the Japanese Society for Familial Tumor. Furthermore, it was adopted also as the clinical important problem of the Japan Endocrine Society, group research also became the 3rd year, and it was required that a clinical practice guideline should have been created immediately. The assignment writer and the assignment writing cooperator were determined as the main item creation of this guideline, Clinical Question (CQ) was created per each item in its duty, and examination was started. CQ, the determination of a proposal, selection of the column, etc. were worked. Determined CQ, columns are 56, 10 in MEN1 and 44, 17 in MEN2, respectively. The recommendation grade based on evidence is due to search literature for every after that CQ proposal, to create a structured abstract, and to be determined from now on. It is thought that completion of this guideline brings a big benefit to what is engaged in the MEN medical examination and research in Japan.

View full abstract

The need for correct and appropriate patient information as well as contact with other sufferers is crucial in the case of rare diseases like multiple endocrine neoplasia (MEN). AMEND believes that an informed patient is more likely to receive the correct care and management from the most appropriate healthcare professional, whilst being in contact with other patients in a similar situation immediately banishes the feeling of loneliness often experienced by people with rare diseases. In order to address these issues, the Association for Multiple Endocrine Neoplasia Disorders (AMEND) was established in 2002 and became a UK registered charitable (not-for-profit) organisation in 2003. AMEND’s aims are to accurately and reliably educate patients and their friends and family about MEN and genetic testing, provide emotional support to families, and to raise awareness of the conditions with the medical profession to aid earlier diagnosis. In the future AMEND hopes that, by working cooperatively with other groups around the world, we will be able to encourage larger scale international research as well as easier access to new treatments.

View full abstract

Lynch syndrome is a hereditary cancer predisposition syndrome inherited in an autosomal dominant manner and associated with deficiency of the mismatch repair (MMR) genes MLH1, MSH2, MSH6 or PMS2. We report a 52-year-old female case of synchronous triple cancers associated with a large deletion in MSH2 gene without a distinct family history of Lynch syndrome. The patient underwent simultaneous operation for cecum cancer, descending colon cancer and endometrial cancer at the age of 52. Due to the presence of MSI-H in resected tumor tissues of all 3 lesions, Lynch syndrome was suspected. Since germline mutation analysis of mismatch repair genes MLH1, MSH2 and MSH6 by direct sequencing showed no deleterious mutation, MLPA analysis of MLH1 and MSH2 was performed and detected a large deletion encompassing exons 14-16 of MSH2. In the context of breakpoint analysis, long-PCR combined with direct sequencing for 3’ downstream of MSH2 was carried out and consequently large deletion 36.7 kb in extent was identified. The mutation found in this study is novel one that has not been reported previously. It seems to be possible to accomplish rational surveillance based on prospect for prognosis and predictive testing for at risk persons by detailed examination of mutations in MMR genes, and that could substantiate a practical management for patients and families.

View full abstract

Lynch Syndrome is an autosomal dominantly inherited disorder showing predisposition to primary cancers from the colorectum, endometrium and other organs. Lynch Syndrome is estimated to account for 2–5% of all colorectal cancers. Cancer predisposing genes of Lynch Syndrome are DNA mismatch repair genes such as MLH1, MSH2, MSH6 and PMS2. Mutations of PMS2 are account for 5% of all mutations in Lynch Syndrome though, due to the difficulties of the analysis by the several pseudogene interferances, there have been hardly any reports of PMS2 analysis in Japanese. We examined the analysis method of PMS2 to establish the genetic testing of PMS2.

View full abstract