Clinical and molecular characteristics of squamous cell carcinomas from Fanconi anemia patients.
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.
van Zeeburg
Hester J T
HJ
Department of Otolaryngology/Head-Neck Surgery, Section Tumor Biology, VU University Medical Center, Amsterdam, the Netherlands.
Snijders
Peter J F
PJ
Wu
Thijs
T
Gluckman
Eliane
E
Soulier
Jean
J
Surralles
Jordi
J
Castella
Maria
M
van der Wal
Jacqueline E
JE
Wennerberg
Johan
J
Califano
Joseph
J
Velleuer
Eunike
E
Dietrich
Ralf
R
Ebell
Wolfram
W
Bloemena
Elisabeth
E
Joenje
Hans
H
Leemans
C René
CR
Brakenhoff
Ruud H
RH
D000328:Adult; D000368:Aged; D001005:Anus Neoplasms / Q000209:etiology; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000821:virology; D004279:DNA, Viral / Q000302:isolation & purification; D004938:Esophageal Neoplasms / Q000209:etiology; D005060:Europe; D005199:Fanconi Anemia / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D005260:Female; D019942:Genes, p16; D016158:Genes, p53; D005833:Genital Neoplasms, Female / Q000209:etiology; D005834:Genital Neoplasms, Male / Q000209:etiology; D006258:Head and Neck Neoplasms / Q000209:etiology; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications; D016133:Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018401:Sample Size; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014412:Tumor Virus Infections / Q000150:complications
D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53