Assessing Genetic Variants of Uncertain Significance: The Example of Lynch Syndrome

TY - ICOMM

T1 - Assessing Genetic Variants of Uncertain Significance: The Example of Lynch Syndrome

AU - Rasmussen, Lene Juel

AU - Heinen, Christopher D.

PY - 2014/4/15

Y1 - 2014/4/15

N2 - A significant fraction of cancer is the result of genetic predisposition. Frequently, in patients with suspected cancer predisposition, subtle variations are found in predisposing genes. Currently, it is often not possible to determine whether such variants are pathogenic, thus they are termed variants of uncertain significance (VUS). This leads to anxiety in carriers and noncarrying relatives alike, as well as to an unnecessary burden to preventive healthcare. The establishment of procedures that enable the diagnostic assessment of VUSs in individuals are discussed and hereditary colorectal cancer syndrome, Lynch syndrome, is used as an example. This challenge is addressed by illustrating the importance of combining genetic and functional data in future strategies to assess VUS. The proposed strategies combine clinical genetic, analytical, functional and in silico approaches.

AB - A significant fraction of cancer is the result of genetic predisposition. Frequently, in patients with suspected cancer predisposition, subtle variations are found in predisposing genes. Currently, it is often not possible to determine whether such variants are pathogenic, thus they are termed variants of uncertain significance (VUS). This leads to anxiety in carriers and noncarrying relatives alike, as well as to an unnecessary burden to preventive healthcare. The establishment of procedures that enable the diagnostic assessment of VUSs in individuals are discussed and hereditary colorectal cancer syndrome, Lynch syndrome, is used as an example. This challenge is addressed by illustrating the importance of combining genetic and functional data in future strategies to assess VUS. The proposed strategies combine clinical genetic, analytical, functional and in silico approaches.

U2 - 10.1002/9780470015902.a0025219

DO - 10.1002/9780470015902.a0025219

M3 - Net publication - Internet publication

ER -