Clinical and molecular characteristics of squamous cell carcinomas from Fanconi anemia patients

Abstract

Fanconi anemia is a recessively inherited disease that is characterized by congenital abnormalities, bone marrow failure, and a predisposition to develop cancer, particularly squamous cell carcinomas (SCCs) in the head and neck and anogenital regions. Previous studies of Fanconi anemia SCCs, mainly from US patients, revealed the presence of high-risk human papillomavirus (HPV) DNA in 21 (84%) of 25 tumors analyzed. We examined a panel of 21 SCCs mainly from European Fanconi anemia patients (n = 19 FA patients; 16 head and neck squamous cell carcinomas [HNSCCs], 2 esophageal SCCs, and 3 anogenital SCCs) for their clinical and molecular characteristics, including patterns of allelic loss, TP53 mutations, and the presence of HPV DNA by GP5+/6+ polymerase chain reaction. HPV DNA was detected in only two (10%) of 21 tumors (both anogenital SCCs) but in none of the 16 HNSCCs. Of the 18 tumors analyzed, 10 contained a TP53 mutation. The patterns of allelic loss were comparable to those generally found in sporadic SCCs. Our data show that HPV does not play a major role in squamous cell carcinogenesis in this cohort of Fanconi anemia patients and that the Fanconi anemia SCCs are genetically similar to sporadic SCCs despite having a different etiology.

Figure 1

Patterns of allelic loss in Fanconi anemia squamous cell carcinomas. All tumors that could be analyzed for allelic imbalances are depicted, including tumors from patients who underwent bone marrow transplantation that could be microdissected without contamination by donor cells (Fa3, Fa8, and Fa17). Also indicated are TP53 mutations, presence of HPV DNA, bone marrow transplantation status, and allelic loss frequency (%: number of markers with allelic loss divided by the total number of informative markers). Black boxes indicate allelic loss (a change in the microsatellite allele ratios of more than 50% in the tumor DNA compared with genetically normal DNA isolated from the stroma), gray boxes indicate no allelic loss, and boxes with diagonal lines indicate microsatellite instability. Presence and absence of a TP53 mutation or HPV DNA in the tumor genome or of receipt of bone marrow transplantation are indicated with + and −, respectively. The specific TP53 mutations are listed in Supplementary Table 2 (available online). XS = chromosome; SCC = squamous cell carcinoma; NI = not informative; NE = not evaluable; ND = not determined; HPV = human papillomavirus; BMT = bone marrow transplant.