Genetics of Endocrine Tumours - Familial Isolated Pituitary Adenoma - FIPA

Plain-language summary

The research is aimed at identifying new predisposition genes for endocrine tumours. Our focus initially is on pituitary adenomas including growth hormone-secreting tumors (somatotrophinomas) and prolactin secreting tumours (prolactinomas), but we wish to extend work to other pituitary tumour cases/families. The recruitment process will be as follows. 1. We will recruit patients from our own Endocrine outpatient clinics and inpatient wards. In addition we will ask colleagues in other Endocrinology Departments (or other specialties such as Clinical Genetics,Pathology, General Medicine ) to identify potentially suitable patients with endocrine \& pituitary tumours from their records. We shall focus on patients with good evidence of inheritance of their condition: relatively early onset; or multiple lesions; or other affected family members. Conditions where the predisposing genes have been identified (principally MEN) will be excluded from study. Patients directly contacting us can also enter the study. 2. The Consultant looking after the patient will contact the patient to initially inform him/her of the study. 3. We will then contact the patient (generally by telephone) to discuss the study and what it would entail in terms of information and samples. 4. Subject to agreement in (3), patient will receive 'Information Sheet for patients with pituitary tumour' and 'Consent Form' and will have blood sampling in Consultant's clinic. 5. We will contact additional family members (if appropriate) after an initial approach by the family member already recruited to the study. The additional family members may have developed tumours similar to those of the proband, or may be unaffected individuals who provide useful information for gene identification purposes (for example, spouses may greatly aid the power of gene mapping by linkage. They will receive the "Information Sheet for family members". analysis). 8\. Archival tissue will be obtained from HTA licensed tissue banks. This is an established bank whose licence is primarily for diagnosis but can be used for research. 9. We will undertake laboratory work, such as genetic linkage analysis, candidate gene mutation screening and studies of loss of heterozygosity in tumours, to identify the genes predisposing to the condition, such as the AIP gene. In addition we would like to screen other genes related to the chaperon AIP molecule, such as AhR, and other genes currently identified (PDE4A5, survivin and Tom20 protein) or may not been identified. Blood samples for DNA and RNA will coded with unique ID numbers. Pituitary and other endocrine tumour samples will be collected at surgery and kept in liquid nitrogen or -80 C. They will be coded with unique ID numbers. Candidate gene sequencing will be performed in the Barts and the London Medical School Genome Centre. RNA expression studies from blood or adenoma tissue samples will be performed by RT-PCR. Protein expression studies will be performed by Western blotting or immunohistochemistry. The first gene we wish to study causes familial acromegaly, a disease resulting from a pituitary adenoma secreting growth hormone. To establish if the candidate gene is also causing possibly sporadic (not familial) cases of the disease, samples (blood and tissue) will be collected from patients with sporadic disease and will be analysed as above.

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