Abstract
AbstractFanconi anemia (FA) is a heritable malformation, bone marrow failure and cancer predisposition syndrome that confers an exceptionally high risk of developing carcinomas arising in squamous mucosal epithelia lining the mouth, proximal esophagus, vulva and anus. The origin of these cancers is not understood, and no effective way has been identified to prevent or delay their appearance. FA-associated carcinomas are also therapeutically challenging, as they may be multi-focal and stage-advanced at diagnosis making surgical control challenging. Moreover, individuals with FA have systemic DNA damage hypersensitivity and thus an elevated risk of toxicity when treated with standard-of-care therapies such as DNA cross-linking drugs and ionizing radiation.We developed the Fanconi Anemia Cancer Cell Line Resource (FA-CCLR) in order to foster new research on the origins, treatment, and prevention of FA-associated cancers. The FA-CCLR consists of FANC-isogenic head and neck squamous cell carcinoma (HNSCC) cell line pairs from cancers arising in individuals with FA, or newly engineered from sporadic HNSCC cell lines. Molecular, cellular, and biochemical analyses were used to demonstrate the causal dependence of key FA-associated phenotypes on FANC genotype, expression and pathway activity. These FANC-isogenic cell line pairs are available to academic and non-profit investigators, with ordering information available at the ‘Fanconi Anemia Research Materials’ Resource and Repository at Oregon Health & Sciences University, Portland OR.SignificanceWe have generated new isogenic cancer cell line models to investigate the origins, treatment and prevention of Fanconi anemia-associated squamous carcinomas that target the oral mucosa, proximal esophagus, and anogenital region.
Publisher
Cold Spring Harbor Laboratory
Reference98 articles.
1. Mehta PA , Ebens C. Fanconi Anemia . In: Adam MP , Ardinger HH , Pagon RA , Wallace SE , Bean LJH , Mirzaa G , et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 2002.
2. The Fanconi Anemia Pathway in Cancer;Annu Rev Cancer Biol,2019
3. Cancer in the National Cancer Institute inherited bone marrow failure syndrome cohort after fifteen years of follow-up
4. Inherited DNA Repair Defects Disrupt the Structure and Function of Human Skin;Cell Stem Cell,2021
5. Lee RH , Kang H , Yom SS , Smogorzewska A , Johnson DE , Grandis JR . Treatment of Fanconi Anemia-Associated Head and Neck Cancer: Opportunities to Improve Outcomes. Clin Cancer Res [Internet]. 2021; Available from: http://dx.doi.org/10.1158/1078-0432.CCR-21-1259