MYCN in human development and diseases.

Area of Science:

• Genetics and Developmental Biology
• Oncology
• Human Pathogenesis

Background:

• Somatic MYCN mutations are key drivers in tumorigenesis, progression, and poor prognosis.
• MYCN's role in human development is increasingly recognized beyond its oncogenic functions.
• MYCN variants are linked to Feingold syndrome type 1 and, recently, megalencephaly-polydactyly syndrome.

Purpose of the Study:

• To explore the involvement of MYCN in human development.
• To elucidate the physiological role of MYCN in human development and pathogenesis.
• To review clinical characteristics of Feingold and megalencephaly-polydactyly syndromes to understand MYCN pathway implications.

Main Methods:

• Review of clinical characteristics of Feingold syndrome and megalencephaly-polydactyly syndrome.
• Analysis of cellular and murine data from loss-of-function (Feingold) and gain-of-function (megalencephaly-polydactyly) models.
• Synthesis of current understanding of MYCN's role in development and disease.

Main Results:

• Gain-of-function MYCN variants (p.(Thr58Met), p.(Pro60Leu)) identified as causative for megalencephaly-polydactyly syndrome.
• Loss-of-function MYCN variants are associated with Feingold syndrome type 1.
• Comparative analysis of syndrome models enhances understanding of MYCN's dual role in development and disease.

Conclusions:

• MYCN plays a critical role in human development, with distinct variants leading to different syndromes.
• Understanding MYCN's physiological functions is crucial for comprehending developmental disorders.
• This review provides insights into the MYCN pathway's broader implications for human health and disease.