Common genetic evolutionary pathways in familial adenomatous polyposis tumors.
Cancer cells progress through the accumulation of genetic alterations. Familial adenomatous polyposis (FAP) tumors provide an excellent model to unravel the molecular steps underlying malignant transformation. Global genomic damage was assessed in 56 adenomas and 3 carcinomas from six FAP patients and compared with that of sporadic adenomas and carcinomas. Evolutive trees were traced after application of maximum likelihood clustering and split decomposition methods to the analysis of comprehensive genetic profiles generated by diverse molecular approaches: arbitrarily primed PCR, comparative genomic hybridization, and flow cytometry. Overall, genomic damage as assessed by arbitrarily primed PCR was lower in familial adenomas than in sporadic adenomas and carcinomas. Comparative genomic hybridization data also show a low number of alterations in the majority of FAP adenomas. Tumors of the same patient were likely to share specific genetic alterations and may be grouped into one or two clusters. Putative common pathways were also identified, which included tumors of up to three different patients. According to our data, FAP tumors accumulate specific genetic alterations and in a preferred order that is characteristic of each individual. Moreover, the particular genetic background and environmental conditions of a FAP patient restrain the molecular evolution portrait of synchronous tumors.
Tarafa
Gemma
G
Laboratori de Recerca Translacional, Institut Català d'Oncologia, Barcelona 08907, Spain.
Prat
Esther
E
Risques
Rosa-Ana
RA
González
Sara
S
Camps
Jordi
J
Grau
Mónica
M
Guinó
Elisabeth
E
Moreno
Víctor
V
Esteller
Manel
M
Herman
James G
JG
Germà
Josep-Ramon
JR
Miró
Rosa
R
Peinado
Miguel Angel
MA
Capellá
Gabriel
G
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000328:Adult; D000368:Aged; D043171:Chromosomal Instability; D019143:Evolution, Molecular; D005260:Female; D005434:Flow Cytometry; D017491:Genes, APC; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D010802:Phylogeny; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic