Genetic Factors and Pheochromocytomas in Neoplasia Type 2 (NEM2A-Pheo)

Genetic Modifying Factors and Pheochromocytomas in Multiple Endocrine Neoplasia Type 2

Multiple endocrine neoplasia type 2A (MEN2A) is a rare syndrome associated with activating mutations in the RET proto-oncogene, combining medullary thyroid cancer in approximately 100% of cases and pheochromocytoma in 10-80% of cases. While it is accepted that the RET mutation causes variable penetrance of pheochromocytoma in the MEN2A patient population, there is no pathophysiological explanation for the phenotypic variability among patients with the same mutation, including within the same family. The aim of this study is to better characterise the genetic factors that may explain the variable penetrance of pheochromocytoma in MEN2. To this end, the investigatoes plan to perform a whole exome analysis in 2 families carrying the p. Cys634Arg mutation causing NEM2A, followed in Marseille by the principal investigator: the 1st family has 11 members all aged over 35 years, for which 8 are carriers of pheochromocytoma while 3 have not developed it (while their age is higher than the latest age of diagnosis of pheochromocytoma in this family); the 2nd family has 3 members (father and daughter with pheochromocytoma developed before 25 years; son without pheochromocytoma at an age of 42 years). The investigators believe that the analysis of these patients should allow the isolation of variants on genes potentially involved in the genesis of a pheochromocytoma in MEN2.

Study Overview

• Status: Recruiting
• Conditions: Pheochromocytoma; Neoplasia

• Study Type: Observational
• Enrollment (Estimated): 14

Contacts and Locations

• Study Contact: Name: Frederic Castinetti; Phone Number: 33 0491384131; Email: frederic.castinetti@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13354
    • Recruiting
    • APHM - Hôpital de la Conception
    • Contact: Frédéric Castinetti; Email: frederic.castinetti@ap-hm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Adult patient followed for familial neoplasia type 2 with or without pheochromocytoma

Description

Inclusion Criteria:

• Patient aged 18 years or older
• Male or female patient
• Patient followed in the investigating department for familial NEM2A C634R (multiple endocrine neoplasia type 2) with or without pheochromocytoma
• Patient affiliated to or benefiting from a social security scheme
• Patient having given his non-opposition to participate in this study
• Patient who has given his consent for the genetic analysis carried out in the framework of the study
• Patient able to understand the purpose of the study

Exclusion Criteria:

• Protected persons (articles L1121-5, L1121-6 and L121-8 of the Public Health Code): pregnant or breastfeeding women, persons deprived of their liberty, under guardianship or curator
• Patients unable to understand the purpose of the study and the information note

Study Plan

How is the study designed?

Design Details

• Observational Models: Family-Based
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic profile	whole-exome analysis between patients with and without pheochromocytoma	Month 0

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Study Director: Francois CREMIEUX, APHM

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2022
• Primary Completion (Estimated): December 14, 2023
• Study Completion (Estimated): December 14, 2023

Study Registration Dates

• First Submitted: December 2, 2021
• First Submitted That Met QC Criteria: December 2, 2021
• First Posted (Actual): December 15, 2021

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: neoplasia; pheochromocytoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Paraganglioma; Neoplasms; Pheochromocytoma
• Other Study ID Numbers: 2020-65

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No