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Fanconi anemia: young patients at high risk for squamous cell carcinoma

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ABSTRACT

Background: Fanconi anemia is one of the best studied inherited cancer-prone diseases. Greatly improved protocols for hematopoietic stem cell transplantation increasingly save the lives of these young patients. However, in both transplanted and not transplanted patients, the emergence of aggressive squamous cell carcinoma represents a major medical challenge.

Conclusions: This mini review summarizes current knowledge about the pathogenesis of squamous cell carcinoma (SCC) in the special context of Fanconi anemia.

No MeSH data available.


Related in: MedlinePlus

Simplified model of the Fanconi anemia pathway. Activation of FANCD2 and FANCI by the FA core complex via monoubiquitination (orange circles) regulates downstream genes involved in recombination repair of DNA crosslinks.
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Fig2: Simplified model of the Fanconi anemia pathway. Activation of FANCD2 and FANCI by the FA core complex via monoubiquitination (orange circles) regulates downstream genes involved in recombination repair of DNA crosslinks.

Mentions: Our current understanding of the role of the FA proteins reflects their pivotal function in the surveillance and maintenance of genomic integrity. As pointed out by Romick-Rosendale and co-workers in a recent review [11], the frequent emergence of SCC in FA must be seen in the context of defective DNA repair compromising genomic integrity. Owing to the rapid pace of FA gene discovery during recent years, the eminent role of FA proteins in recombinational types of DNA repair has emerged (cf. Figure 2). Briefly, in response to crosslink type of DNA damage and stalled replication forks, eight of the known FA proteins assemble into the so-called FA core complex which leads to the activation (via monoubiquitination) of the FANCD2 and FANCI proteins and, in turn, to the activation of a number of ‘downstream’ proteins instrumental in DNA repair. Interestingly, monoallelic mutations in some of the downstream proteins are known to confer a high risk of breast cancer (e.g., FANCD1 = BRCA2, FANCN = PALPB2, FANCJ = BRIP1, FANCO = RAD51C). Again, these observations emphasize the intimate connection between inadequate or failing DNA maintenance and the emergence of neoplasia. Persistent or misrepaired DNA damage results in cell cycle arrest, apoptosis, and chromosomal instability and, ultimately, in the complex patterns of somatic mutations and epimutations which characterize malignant cell populations.Figure 2


Fanconi anemia: young patients at high risk for squamous cell carcinoma
Simplified model of the Fanconi anemia pathway. Activation of FANCD2 and FANCI by the FA core complex via monoubiquitination (orange circles) regulates downstream genes involved in recombination repair of DNA crosslinks.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530570&req=5

Fig2: Simplified model of the Fanconi anemia pathway. Activation of FANCD2 and FANCI by the FA core complex via monoubiquitination (orange circles) regulates downstream genes involved in recombination repair of DNA crosslinks.
Mentions: Our current understanding of the role of the FA proteins reflects their pivotal function in the surveillance and maintenance of genomic integrity. As pointed out by Romick-Rosendale and co-workers in a recent review [11], the frequent emergence of SCC in FA must be seen in the context of defective DNA repair compromising genomic integrity. Owing to the rapid pace of FA gene discovery during recent years, the eminent role of FA proteins in recombinational types of DNA repair has emerged (cf. Figure 2). Briefly, in response to crosslink type of DNA damage and stalled replication forks, eight of the known FA proteins assemble into the so-called FA core complex which leads to the activation (via monoubiquitination) of the FANCD2 and FANCI proteins and, in turn, to the activation of a number of ‘downstream’ proteins instrumental in DNA repair. Interestingly, monoallelic mutations in some of the downstream proteins are known to confer a high risk of breast cancer (e.g., FANCD1 = BRCA2, FANCN = PALPB2, FANCJ = BRIP1, FANCO = RAD51C). Again, these observations emphasize the intimate connection between inadequate or failing DNA maintenance and the emergence of neoplasia. Persistent or misrepaired DNA damage results in cell cycle arrest, apoptosis, and chromosomal instability and, ultimately, in the complex patterns of somatic mutations and epimutations which characterize malignant cell populations.Figure 2

View Article: PubMed Central

ABSTRACT

Background: Fanconi anemia is one of the best studied inherited cancer-prone diseases. Greatly improved protocols for hematopoietic stem cell transplantation increasingly save the lives of these young patients. However, in both transplanted and not transplanted patients, the emergence of aggressive squamous cell carcinoma represents a major medical challenge.

Conclusions: This mini review summarizes current knowledge about the pathogenesis of squamous cell carcinoma (SCC) in the special context of Fanconi anemia.

No MeSH data available.


Related in: MedlinePlus