Cytogenetic characteristics of oral squamous cell carcinomas in Fanconi anemia.
Fanconi anemia (FA) is an autosomal recessive syndrome with a marked predisposition to malignancies, in particular acute myeloid leukemia and squamous cell carcinoma of the oral cavity. We examined oral squamous cell carcinoma tissue from two FA patients (FA-A and FA-C) by comparative genomic hybridization. Both tumors, which were negative for human papilloma as well as Epstein-Barr viral sequences, showed multiple alterations with a high proportion of whole-arm chromosomal gains and losses. This combination of features as well as the sites involved in chromosomal breakage are very similar to what is typically observed in non-FA oral tumors. These results suggest that the process leading to early occurrence of oral cancer in FA patients follows a similar pathway as in non-FA cancer patients, which would support a caretaker function for FA genes in the protection against oral carcinogenesis. Since FA patients are uniquely hypersensitive to DNA cross-linking agents, while oral cancer in the general population is thought to be environmentally induced, these results also suggest that environmental DNA cross-linkers may be causally involved in oral carcinogenesis.
Department of Pathology, Free University Medical Center, Amsterdam, The Netherlands.
M A
MA
Hermsen
Y
Y
Xie
M A
MA
Rooimans
G A
GA
Meijer
J P
JP
Baak
J T
JT
Plukker
F
F
Arwert
H
H
Joenje
D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000235:genetics*; D002869:Chromosome Aberrations; D005199:Fanconi Anemia / Q000150:complications / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D016368:Frameshift Mutation; D006801:Humans; D007621:Karyotyping; D009062:Mouth Neoplasms / Q000150:complications / Q000235:genetics*