TY - JOUR
T1 - Counting alleles reveals a connection between chromosome 18q loss and vascular invasion
AU - Zhou, Wei
AU - Galizia, Gennaro
AU - Goodman, Steven N.
AU - Romans, Katharine E.
AU - Kinzler, Kenneth W.
AU - Vogelstein, Bert
AU - Choti, Michael A.
AU - Montgomery, Elizabeth A.
N1 - Funding Information:
The financial support from the Heidelberger Akademie der Wissenschaften (Germany) is gratefully acknowledged. We wish to thank M. Little for support, M. Bechtel from Genzyme Virotech GmbH for supplying the tetanus toxin, and Olaf Broders for helping with the experimental work. We are grateful for E.K.F. Bautz for his continuous support and suggestions.
Funding Information:
This work is supported by NIH grant CA62924 and CA43460. Under a licensing agreement between the Johns Hopkins University and EXACT Laboratories, Inc., Digital PCR technology was licensed to EXACT, and Drs. Vogelstein and Kinzler are entitled to a share of royalties received by the University from sales of the licensed technology. The terms of these arrangements are being managed by the university in accordance with its conflict of interest policies.
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - The analysis of loss of heterozygosity (LOH) is perhaps the most widely used technique in cancer genetics. In primary tumors, however, the analysis of LOH is fraught with technical problems that have limited its reproducibility and interpretation. In particular, tumors are mixtures of neoplastic and nonneoplastic cells, and the DNA from the nonneoplastic cells can mask LOH. We here describe a new experimental approach, involving two components, to overcome these problems. First, a form of digital PCR1 was employed to directly count, one by one, the number of each of the two alleles in tumor samples. Second, Bayesian-type likelihood methods were used to measure the strength of the evidence for the allele distribution being different from normal. This approach imparts a rigorous statistical basis to LOH analyses, and should be able to provide more reliable information than heretofore possible in LOH studies of diverse tumor types.
AB - The analysis of loss of heterozygosity (LOH) is perhaps the most widely used technique in cancer genetics. In primary tumors, however, the analysis of LOH is fraught with technical problems that have limited its reproducibility and interpretation. In particular, tumors are mixtures of neoplastic and nonneoplastic cells, and the DNA from the nonneoplastic cells can mask LOH. We here describe a new experimental approach, involving two components, to overcome these problems. First, a form of digital PCR1 was employed to directly count, one by one, the number of each of the two alleles in tumor samples. Second, Bayesian-type likelihood methods were used to measure the strength of the evidence for the allele distribution being different from normal. This approach imparts a rigorous statistical basis to LOH analyses, and should be able to provide more reliable information than heretofore possible in LOH studies of diverse tumor types.
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U2 - 10.1038/83572
DO - 10.1038/83572
M3 - Article
C2 - 11135558
AN - SCOPUS:0035174837
SN - 1087-0156
VL - 19
SP - 78
EP - 81
JO - Nature biotechnology
JF - Nature biotechnology
IS - 1
ER -