Interrogation of genomes by molecular copy-number counting (MCC).
Human cancers and some congenital traits are characterized by cytogenetic aberrations including translocations, amplifications, duplications or deletions that can involve gain or loss of genetic material. We have developed a simple method to precisely delineate such regions with known or cryptic genomic alterations. Molecular copy-number counting (MCC) uses PCR to interrogate miniscule amounts of genomic DNA and allows progressive delineation of DNA content to within a few hundred base pairs of a genomic alteration. As an example, we have located the junctions of a recurrent nonreciprocal translocation between chromosomes 3 and 5 in human renal cell carcinoma, facilitating cloning of the breakpoint without recourse to genomic libraries. The analysis also revealed additional cryptic chromosomal changes close to the translocation junction. MCC is a fast and flexible method for characterizing a wide range of chromosomal aberrations.
Daser
Angelika
A
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
Thangavelu
Madan
M
Pannell
Richard
R
Forster
Alan
A
Sparrow
Louise
L
Chung
Grace
G
Dear
Paul H
PH
Rabbitts
Terence H
TH
D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D004252:DNA Mutational Analysis / Q000379:methods; D018628:Gene Dosage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*