Mutational load distribution analysis yields metrics reflecting genetic instability during pancreatic carcinogenesis.
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.
Tarafa
Gemma
G
Departments of Pathology and Internal Medicine/Digestive Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
Tuck
David
D
Ladner
Daniela
D
Topazian
Mark
M
Brand
Randall
R
Deters
Carolyn
C
Moreno
Victor
V
Capella
Gabriel
G
Lynch
Henry
H
Lizardi
Paul
P
Costa
Jose
J
D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D019295:Computational Biology; D006801:Humans; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics*; D017422:Sequence Analysis, DNA