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Mutational heterogeneity in cancer and the search for new cancer-associated genes
Michael S. Lawrence*, Petar Stojanov*, Paz Polak*, Gregory V. Kryukov, Kristian Cibulskis, Andrey Sivachenko, Scott L. Carter, Chip Stewart, Craig H. Mermel, Steven A. Roberts, Adam Kiezun, Peter S.…
Mutational heterogeneity in cancer and the search for new cancer genes
A fundamental problem with cancer genome studies is described: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds and the list includes many implausible genes, suggesting extensive false-positive findings that overshadow true driver events.
Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing
- J. Lohr, P. Stojanov, +31 authors T. Golub
- Biology, MedicineProceedings of the National Academy of Sciences
- 17 February 2012
It is shown that BCL2 mutations commonly occur in patients with BCL 2/IgH rearrangements as a result of somatic hypermutation normally occurring at the IgH locus, and an algorithm designed to identify likely functionally relevant but infrequent mutations is identified as likely drivers of DLBCL pathogenesis in some patients.
Landscape of Somatic Retrotransposition in Human Cancers
Analyzing five cancer types occurring among several individuals found that three types of epithelial tumors exhibited high rates of element movement relative to brain and blood cancers, and Whole-genome sequencing provides evidence for somatic insertions in colorectal, prostate, and ovarian cancers.
Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy.
We performed massively parallel sequencing of paired tumor/normal samples from 203 multiple myeloma (MM) patients and identified significantly mutated genes and copy number alterations and discovered…
Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors
- V. Adalsteinsson, G. Ha, +54 authors M. Meyerson
- Medicine, BiologyNature Communications
- 1 November 2017
The authors provide methods to identify patients eligible for comprehensive cfDNA profiling, revealing its applicability to many patients, and demonstrate high concordance of cfDNA and metastatic tumor whole-exome sequencing.
Regulatory T cells in the periphery
It is shown that interleukin‐2 (IL‐2) enhances the development of effector cells and is essential for the peripheral generation of regulatory cells.
Whole exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer
This study reports an integrated process to isolate, qualify and sequence whole exomes of CTCs with high fidelity using a census-based sequencing strategy and establishes a foundation for CTC genomics in the clinic.
An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia
A role for epigenetic heterogeneity in leukemia resistance is established that may be addressed by incorporating epigenetic modulators in combination therapy, and the GSI-JQ1 combination was found to be effective against primary human leukemias in vivo.
Sequential development of interleukin 2–dependent effector and regulatory T cells in response to endogenous systemic antigen
- B. Knoechel, J. Lohr, E. Kahn, J. Bluestone, A. Abbas
- Biology, MedicineThe Journal of experimental medicine
- 21 November 2005
A peripheral T cell reaction to a systemic antigen goes through a phase of effector cell–mediated pathology followed by T reg cell-mediated recovery, and both require the growth factor IL-2.