Abstract
Considering carcinogenesis as a microevolutionary process, best described in the context of metapopulation dynamics, provides the basis for theoretical and empirical studies that indicate it is possible to estimate the relative contribution of genetic instability and selection to the process of tumor formation. We show that mutational load distribution analysis (MLDA) of DNA found in pancreatic fluids yields biometrics that reflect the interplay of instability, selection, accident, and gene function that determines the eventual emergence of a tumor. An in silico simulation of carcinogenesis indicates that MLDA may be a suitable tool for early detection of pancreatic cancer. We also present evidence indicating that, when performed serially in individuals harboring a p16 germ-line mutation bestowing a high risk for pancreatic cancer, MLDA may be an effective tool for the longitudinal assessment of risk and early detection of pancreatic cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 4306-4311 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 105 |
| Issue number | 11 |
| DOIs | |
| State | Published - Mar 18 2008 |
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All Science Journal Classification (ASJC) codes
- Genetics
- General
Cite this
Mutational load distribution analysis yields metrics reflecting genetic instability during pancreatic carcinogenesis. / Tarafa, Gemma; Tuck, David; Ladner, Daniela; Topazian, Mark; Brand, Randall; Deters, Carolyn; Moreno, Victor; Capella, Gabriel; Lynch, Henry T.; Lizardi, Paul; Costa, Jose.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 11, 18.03.2008, p. 4306-4311.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mutational load distribution analysis yields metrics reflecting genetic instability during pancreatic carcinogenesis
AU - Tarafa, Gemma
AU - Tuck, David
AU - Ladner, Daniela
AU - Topazian, Mark
AU - Brand, Randall
AU - Deters, Carolyn
AU - Moreno, Victor
AU - Capella, Gabriel
AU - Lynch, Henry T.
AU - Lizardi, Paul
AU - Costa, Jose
PY - 2008/3/18
Y1 - 2008/3/18
N2 - Considering carcinogenesis as a microevolutionary process, best described in the context of metapopulation dynamics, provides the basis for theoretical and empirical studies that indicate it is possible to estimate the relative contribution of genetic instability and selection to the process of tumor formation. We show that mutational load distribution analysis (MLDA) of DNA found in pancreatic fluids yields biometrics that reflect the interplay of instability, selection, accident, and gene function that determines the eventual emergence of a tumor. An in silico simulation of carcinogenesis indicates that MLDA may be a suitable tool for early detection of pancreatic cancer. We also present evidence indicating that, when performed serially in individuals harboring a p16 germ-line mutation bestowing a high risk for pancreatic cancer, MLDA may be an effective tool for the longitudinal assessment of risk and early detection of pancreatic cancer.
AB - Considering carcinogenesis as a microevolutionary process, best described in the context of metapopulation dynamics, provides the basis for theoretical and empirical studies that indicate it is possible to estimate the relative contribution of genetic instability and selection to the process of tumor formation. We show that mutational load distribution analysis (MLDA) of DNA found in pancreatic fluids yields biometrics that reflect the interplay of instability, selection, accident, and gene function that determines the eventual emergence of a tumor. An in silico simulation of carcinogenesis indicates that MLDA may be a suitable tool for early detection of pancreatic cancer. We also present evidence indicating that, when performed serially in individuals harboring a p16 germ-line mutation bestowing a high risk for pancreatic cancer, MLDA may be an effective tool for the longitudinal assessment of risk and early detection of pancreatic cancer.
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UR - http://www.scopus.com/inward/citedby.url?scp=41949112661&partnerID=8YFLogxK
U2 - 10.1073/pnas.0708250105
DO - 10.1073/pnas.0708250105
M3 - Article
VL - 105
SP - 4306
EP - 4311
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 11
ER -