Nancy L Parmalee
Research Subjects
Nancy L Parmalee has a total of 40 co-authors. Here are the top co-authors by number of shared publications:
- Adriana Estela Sedeño Cortés
Division of Medical Genetics, University of Washington
1 shared publication - Andrew Stergachis
Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA
1 shared publication - Anna Minkina
Department of Genome Sciences, University of Washington
1 shared publication Brianne Carroll
1 shared publication- Caitlin N. Jacques
Molecular Plant Sciences Graduate Program (D.S.F., C.N.J., K.N.L., J.Z., M.M.N.) and Department of Crop and Soil Sciences (D.S.F., C.N.J., J.Z., M.M.N.), Washington State University, Pullman, Washington 99164; andRIKEN Center for Sustainable Resource Science, Tsurumi, Yokohama, Kanagawa 230-0045, Japan (A.I., K.S.).
1 shared publication - Chia-Lin Wei
The Jackson Laboratory for Genomic Medicine, Farmington, USA
1 shared publication
Latest Publications
- Open Access
A telomere-to-telomere map of somatic mutation burden and functional impact in cancer
Oncogenesis involves widespread genetic and epigenetic alterations, yet the full spectrum of somatic variation genome-wide remains unresolved. We generated a near-telomere-to-telomere (T2T) diploid assembly of a donor paired with deep short- and long-read sequencing of their melanoma. This revealed that 16% of somatic variants occur in sequences absent from GRCh38, with satellite repeats acting as hotspots for UV-induced damage due to sequence-intrinsic mutability and inefficient repair. Centromere kinetochore domains emerged as focal sites of structural, genetic, and epigenetic variation, leading to remodeling of centromere kinetochore binding domains during tumor evolution. Single-molecule telomere reconstructions uncovered cycles of attrition, deletion, and telomerase-mediated extension that shape cancer telomeres. Finally, diploid chromatin maps exposed that copy number alterations and epimutations, rather than point mutations, predominate in rewiring cancer regulatory programs. These findings define the full landscape of a cancer’s somatic variation and their functional impact, establishing a blueprint for T2T studies of mosaicism.
Open AccessA telomere-to-telomere map of somatic mutation burden and functional impact in cancer
Oncogenesis involves widespread genetic and epigenetic alterations, yet the full spectrum of somatic variation genome-wide remains unresolved. We generated a near-telomere-to-telomere (T2T) diploid assembly of a donor paired with deep short- and long-read sequencing of their melanoma. This revealed that 16% of somatic variants occur in sequences absent from GRCh38, with satellite repeats acting as hotspots for UV-induced damage due to sequence-intrinsic mutability and inefficient repair. Centromere kinetochore domains emerged as focal sites of structural, genetic, and epigenetic variation, leading to remodeling of centromere kinetochore binding domains during tumor evolution. Single-molecule telomere reconstructions uncovered cycles of attrition, deletion, and telomerase-mediated extension that shape cancer telomeres. Finally, diploid chromatin maps exposed that copy number alterations and epimutations, rather than point mutations, predominate in rewiring cancer regulatory programs. These findings define the full landscape of a cancer’s somatic variation and their functional impact, establishing a blueprint for T2T studies of mosaicism.