Fanconi anemia (FA) is a rare human genetic disease caused by mutations in any 
one of 13 known genes that encode proteins functioning in one common signaling 
pathway, the FA pathway, or in unknown genes. One characteristic of FA is an 
extremely high incidence of cancer, indicating the importance of the FA pathway 
in tumor suppression. However, the role of this pathway in the development and 
progression of human cancers in individuals who do not have FA has not been 
clearly determined. Here, we report that elevated expression of what we believe 
to be a novel splice variant of FA complementation group L (FANCL), which we 
identified and named FAVL, can impair the FA pathway in non-FA human tumor cells 
and act as a tumor promoting factor. FAVL expression was elevated in half of the 
human carcinoma cell lines and carcinoma tissue samples tested. Expression of 
FAVL resulted in decreased FANCL expression by sequestering FANCL to the 
cytoplasm and enhancing its degradation. Importantly, this impairment of the FA 
pathway by FAVL elevation provided human cancer cells with a growth advantage, 
caused chromosomal instability in vitro, and promoted tumor development in a 
xenograft mouse model. These data indicate that FAVL impairment of the FA 
pathway likely contributes to the development of non-FA human cancers and 
therefore add a challenging layer of complexity to the pathogenesis of human 
cancer. We further believe that these data will prove useful for developing 
additional tools for fighting human cancer.