Abstract

Ras genes are the most common targets for somatic gain-of-function mutations in human cancer. Recently, germline mutations that affect components of the Ras–Raf–mitogen-activated and extracellular-signal regulated kinase kinase (MEK)–extracellular signal-regulated kinase (ERK) pathway were shown to cause several developmental disorders, including Noonan, Costello and cardio-facio-cutaneous syndromes. Many of these mutant alleles encode proteins with aberrant biochemical and functional properties. Here we will discuss the implications of germline mutations in the Ras–Raf–MEK–ERK pathway for understanding normal developmental processes and cancer pathogenesis.

Author affiliations

1. Department of Pediatrics, University of California, 513 Parnassus Avenue, Room HSE-302, San Francisco, California 94143, USA.
2. Comprehensive Cancer Center, University of California, 513 Parnassus Avenue, Room HSE-302, San Francisco, California 94143, USA.
3. Plexxikon Inc., 91 Bolivar Drive, Berkeley, California 94710, USA.

Correspondence to: Gideon Bollag³ Email: gbollag@plexxikon.com

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