Johns Hopkins University

Tian-li Wang

Bert Vogelstein

Kenneth W Kinzler

Victor E Velculescu

Alberto Bardelli

Yardena Samuels

Christopher Lengauer

Donald William Parsons

Given the important role of protein kinases in pathways affecting cellular growth and invasion, we have analyzed 340 serine/threonine kinases for genetic mutations in colorectal cancers. Mutations in eight genes were identified, including three members of the phosphatidylinositol-3-kinase (PI3K) pathway; the alterations in the latter genes each occurred in different tumors and did not overlap with mutations in PIK3CA or other non-serine-threonine kinase (STK) members of the PI3K pathway, suggesting that mutations in any of these genes had equivalent tumorigenic effects. These data demonstrate that the PI3K pathway is a major target for mutational activation in colorectal cancers and provide new opportunities for therapeutic intervention.

P13K pathway mutations in cancer

Alterations in the genetic content of a cell underlie many human diseases, including cancers. A method called Digital Karyotyping provides quantitative analysis of DNA copy number at high resolution. This approach involves the isolation and enumeration of short sequence tags from specific genomic loci. Analysis of human cancer cells using this method identified gross chromosomal changes as well as amplifications and deletions, including regions not previously known to be altered. Foreign DNA sequences not present in the normal human genome could also be readily identified. Digital Karyotyping provides a broadly applicable means for systematic detection of DNA copy number changes on a genomic scale.

Digital karyotyping

Growing community of inventors

Baltimore, MD, United States of America

Tian-li Wang