Institution
Cold Spring Harbor Laboratory
Nonprofit•Cold Spring Harbor, New York, United States•
About: Cold Spring Harbor Laboratory is a nonprofit organization based out in Cold Spring Harbor, New York, United States. It is known for research contribution in the topics: Gene & Genome. The organization has 3772 authors who have published 6603 publications receiving 1010873 citations. The organization is also known as: CSHL.
Papers published on a yearly basis
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TL;DR: It is shown that with flow-sorted nuclei, whole genome amplification and next generation sequencing the authors can accurately quantify genomic copy number within an individual nucleus and indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.
Abstract: Genomic analysis provides insights into the role of copy number variation in disease, but most methods are not designed to resolve mixed populations of cells. In tumours, where genetic heterogeneity is common, very important information may be lost that would be useful for reconstructing evolutionary history. Here we show that with flow-sorted nuclei, whole genome amplification and next generation sequencing we can accurately quantify genomic copy number within an individual nucleus. We apply single-nucleus sequencing to investigate tumour population structure and evolution in two human breast cancer cases. Analysis of 100 single cells from a polygenomic tumour revealed three distinct clonal subpopulations that probably represent sequential clonal expansions. Additional analysis of 100 single cells from a monogenomic primary tumour and its liver metastasis indicated that a single clonal expansion formed the primary tumour and seeded the metastasis. In both primary tumours, we also identified an unexpectedly abundant subpopulation of genetically diverse 'pseudodiploid' cells that do not travel to the metastatic site. In contrast to gradual models of tumour progression, our data indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.
2,426 citations
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TL;DR: It is reported here that the T antigen in a line of SV40-transformed mouse cells forms an oligomeric complex with a specific cell coded protein.
Abstract: THE early region of the small DNA tumour virus, simian virus 40 (SV40), is known to code for at least two polypeptides, the t and T antigens (‘small t’ and ‘large T’) Both these polypeptides are expressed in cells transformed by the virus1–4, and the T antigen has been shown to be essential for both the initiation and maintenance of the transformed state5–9 We therefore need to know how this T protein interacts with components of the host cell in order to understand the mechanism of SV40-induced transformation We report here that the T antigen in a line of SV40-transformed mouse cells forms an oligomeric complex with a specific cell coded protein
2,400 citations
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TL;DR: Human cell lines that expressed hTR mutated in the template region generated the predicted mutant telomerase activity, and cells transfected with an antisense hTR lost telomeric DNA and began to die after 23 to 26 doublings.
Abstract: Eukaryotic chromosomes are capped with repetitive telomere sequences that protect the ends from damage and rearrangements. Telomere repeats are synthesized by telomerase, a ribonucleic acid (RNA)-protein complex. Here, the cloning of the RNA component of human telomerase, termed hTR, is described. The template region of hTR encompasses 11 nucleotides (5'-CUAACCCUAAC) complementary to the human telomere sequence (TTAGGG)n. Germline tissues and tumor cell lines expressed more hTR than normal somatic cells and tissues, which have no detectable telomerase activity. Human cell lines that expressed hTR mutated in the template region generated the predicted mutant telomerase activity. HeLa cells transfected with an antisense hTR lost telomeric DNA and began to die after 23 to 26 doublings. Thus, human telomerase is a critical enzyme for the long-term proliferation of immortal tumor cells.
2,305 citations
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TL;DR: This work investigates how inhibition of the widely expressed transcriptional coactivator BRD4 leads to selective inhibition ofThe MYC oncogene in multiple myeloma (MM), and finds that super-enhancers were found at key oncogenic drivers in many other tumor cells.
2,292 citations
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TL;DR: Understanding the molecular events that contribute to drug-induced apoptosis, and how tumors evade apoptotic death, provides a paradigm to explain the relationship between cancer genetics and treatment sensitivity and should enable a more rational approach to anticancer drug design and therapy.
2,281 citations
Authors
Showing all 3800 results
Name | H-index | Papers | Citations |
---|---|---|---|
Phillip A. Sharp | 172 | 614 | 117126 |
Gregory J. Hannon | 165 | 421 | 140456 |
Ian A. Wilson | 158 | 971 | 98221 |
Marco A. Marra | 153 | 620 | 184684 |
Michael E. Greenberg | 148 | 316 | 114317 |
Tom Maniatis | 143 | 318 | 299495 |
Detlef Weigel | 142 | 516 | 84670 |
Kim Nasmyth | 142 | 294 | 59231 |
Arnold J. Levine | 139 | 485 | 116005 |
Joseph E. LeDoux | 139 | 478 | 91500 |
Gerald R. Fink | 138 | 316 | 70868 |
Ramnik J. Xavier | 138 | 597 | 101879 |
Harold E. Varmus | 137 | 496 | 76320 |
David A. Jackson | 136 | 1095 | 68352 |
Scott W. Lowe | 134 | 396 | 89376 |