Abstract:
:Genetic mutations in BRCA1, which is crucial for the process of DNA repair and maintenance of genomic integrity, are known to increase markedly the risk of breast and ovarian cancers. Clinical genetic testing has been used to identify new BRCA1 variants; however, functional assessment and determination of their pathogenicity still poses challenges for clinical management. Here, we describe that CRISPR-mediated cytosine base editor, known as BE3, can be used for the functional analysis of BRCA1 variants. We performed CRISPR-mediated base-editing screening using 745 gRNAs targeting all exons in BRCA1 to identify loss-of-function variants and identified variants whose function has heretofore remained unknown, such as c.-97C>T, c.154C>T, c.3847C>T, c.5056C>T, and c.4986+5G>A. Our results show that CRISPR-mediated base editor is a powerful tool for the reclassification of variants of uncertain significance (VUSs) in BRCA1.
journal_name
Oncogenejournal_title
Oncogeneauthors
Kweon J,Jang AH,Shin HR,See JE,Lee W,Lee JW,Chang S,Kim K,Kim Ydoi
10.1038/s41388-019-0968-2subject
Has Abstractpub_date
2020-01-01 00:00:00pages
30-35issue
1eissn
0950-9232issn
1476-5594pii
10.1038/s41388-019-0968-2journal_volume
39pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::The myb proto oncogene product (c-Myb) is a transcriptional regulator and its expression and function are tightly linked to the cellular entry into S phase and DNA synthesis. It has been shown [Venturelli, D., Travali, S. & Calabretta, B. (1990). Proc. Natl. Acad. Sci. USA, 87, 5963-5967] that inhibition of T-cell pro...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-10-01 00:00:00
abstract::The p53/p21Cip1/Waf1-dependent checkpoint control of G1/S and G2/M phases of the cell cycle in response to DNA damage is an important mechanism of genome stability maintenance in normal cells. In many tumor cells, due to frequent point mutations and deletions of p53, the stringent control of the cell cycle and apoptos...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202945
更新日期:1999-10-07 00:00:00
abstract::Pdcd4 is a novel transformation suppressor that is highly expressed in promotion-resistant (P-) mouse epidermal JB6 cells but not in susceptible (P+) cells. Overexpression of pdcd4 cDNA in stably transfected P+ cells rendered cells resistant to tumor promoter-induced transformation, indicating that elevated expression...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204137
更新日期:2001-02-08 00:00:00
abstract::Frequent allelic losses of chromosome 3p in lung cancer have been reported in a number of studies, and we previously demonstrated that 3p21.3 is one of the common regions of deletion in lung cancers and renal cell carcinomas. To further define a region containing the putative tumor suppressor gene, we performed Southe...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
abstract::Galectin-3 is a multifunctional carbohydrate-binding protein found in the nucleus, cytoplasm and the extracellular milieu. Nuclear galectin-3 expression is associated with cell proliferation, and its role in pre-mRNA splicing has been suggested. In this report, we investigated the role of galectin-3 on cyclin D(1) gen...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205820
更新日期:2002-11-14 00:00:00
abstract::Infection by HTLV-1 has been correlated with the appearance of various proliferative or degenerative diseases. Some of these disorders have been observed in transgenic mice expressing the Tax protein, which is known to transactivate various viral and cellular promoters through interactions with several transcription f...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201567
更新日期:1998-02-05 00:00:00
abstract::The ARF tumour suppressor protein plays a critical role in the activation of p53 in response to oncogenic stress. ARF can activate p53 through nucleolar sequestration of Mdm2. However, several lines of evidence indicate that this is not the only way of action of ARF, and alternative mechanisms must exist. p33ING1 is a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209526
更新日期:2006-08-24 00:00:00
abstract::The C3H/HeJ (C3H), A/J and BALB/cByJ (BALB) mouse strains are respectively resistant, sensitive and intermediate regarding the induction of lung tumors by urethane. The phenotypic difference between C3H and A/J is largely determined by the Pas1 (Pulmonary adenoma susceptibility 1) gene on chromosome 6, the A/J allele ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201357
更新日期:1997-10-09 00:00:00
abstract::There is increasing evidence that mast cells (MCs) and their mediators are involved in the remodeling of the tumor microenvironment and promote tumor growth, angiogenesis and metastasis. We have found that an increased density of MCs in thyroid cancer (TC) correlates with enhanced invasiveness. However, the MC-derived...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.441
更新日期:2015-10-01 00:00:00
abstract::P21waf1/cip1 is a potent inhibitor of cell cycle progression and can inhibit the growth of both normal cells and cells transformed by a number of oncogenes. However, the ability of p21waf1/cip1 to inhibit the growth of cells that overexpress the transcriptional transactivator E2F1 is controversial: it has been reporte...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201849
更新日期:1998-06-18 00:00:00
abstract::The BCL6 gene, mapped at the chromosomal band 3q27, encodes a POZ/Zinc finger transcription repressor protein. It is frequently activated in Non-Hodgkin's lymphomas (NHL) by translocations with breakpoints clustering in the 5' major breakpoint region (MBR) as well as by mutations in the same region. The translocations...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202098
更新日期:1998-10-01 00:00:00
abstract::Early growth response-1 (Egr-1) is overexpressed in human prostate tumors and contributes to cancer progression. On the other hand, mutation of p53 is associated with advanced prostate cancer, as well as with metastasis and hormone independence. This study shows that in prostate cell lines in culture, Egr-1 overexpres...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.24
更新日期:2010-05-06 00:00:00
abstract::FHIT (Fragile Histidine Triad), a putative tumor suppressor gene, was cloned from fetal brain and colon cDNA libraries. Portions of this gene are deleted in esophageal, colon, lung and breast tumors, but this gene has not been found altered in sporadic renal cell carcinomas. We report here an alternatively spliced for...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201164
更新日期:1997-07-03 00:00:00
abstract::In this study, we show that the ETS transcription factor ER81 directly binds to and activates the promoter of the matrix metalloproteinase gene, MMP-1. Further, the oncoprotein HER2/Neu synergizes with ER81 to stimulate MMP-1 transcription. The activation of ER81 by HER2/Neu is mediated by MAP kinases, which phosphory...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204820
更新日期:2001-09-27 00:00:00
abstract::Cell cycle checkpoints and tumor suppressor gene functions appear to be required for the maintenance of a stable genome in proliferating cells. In this study chromosomal destabilization was monitored in relation to telomere structure, lifespan control and G2 checkpoint function. Replicative senescence was inactivated ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201711
更新日期:1998-04-09 00:00:00
abstract::Loss of growth control and a marked resistance to apoptosis are considered major mechanisms driving tumour progression. Protein kinases C (PKC) have been shown to be important in the regulation of proliferation and apoptosis. In this report, we investigated the role of the PKC-like kinase PKCmu in the control of these...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207001
更新日期:2003-12-04 00:00:00
abstract::Targeting Bruton tyrosine kinase (BTK) by ibrutinib is an effective treatment for patients with relapsed/refractory mantle cell lymphoma (MCL). However, both primary and acquired resistance to ibrutinib have developed in a significant number of these patients. A combinatory strategy targeting multiple oncogenic pathwa...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.155
更新日期:2016-12-01 00:00:00
abstract::Procollagen lysyl hydroxylase 1 (PLOD1) is highly expressed in malignant tumors such as esophageal squamous cell carcinoma, gastric cancer, and colorectal cancer. Bioinformatics analysis revealed that PLOD1 is associated with the progression of GBM, particularly the most malignant mesenchymal subtype (MES). Moreover, ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-01635-y
更新日期:2021-01-08 00:00:00
abstract::Checkpoint protein Chk1 has been identified as an Hsp90 client. Treatment with 100 nM geldanamycin (GM) for 24 h markedly reduced the Chk1 amount in Jurkat and ML-1 leukemia cell lines. Because Chk1 plays a central role in G2 checkpoint, we added GM to G2-arrested Jurkat and HL-60 cells pretreated with 50 nM doxorubic...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210978
更新日期:2008-05-15 00:00:00
abstract::The crizotinib-resistant ALK(F1174L) mutation arises de novo in neuroblastoma (NB) and is acquired in ALK translocation-driven cancers, lending impetus to the development of novel anaplastic lymphoma kinase (ALK) inhibitors with different modes of action. The diaminopyrimidine TAE684 and its derivative ceritinib (LDK3...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.434
更新日期:2016-07-14 00:00:00
abstract::Cbl-b, a mammalian homolog of Cbl, consists of an N-terminal region (Cbl-b-N) highly homologous to oncogenic v-Cbl, a Ring finger, and a C-terminal region containing multiple proline-rich stretches and potential tyrosine phosphorylation sites. In the present study, we demonstrate that upon engagement of the T cell rec...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202411
更新日期:1999-02-04 00:00:00
abstract::Approximately 80% of breast cancers express the estrogen receptor-alpha (ERalpha) and are treated with anti-estrogens. Resistance to these agents is a major cause of mortality. We have shown that estrogen inhibits Notch, whereas anti-estrogens or estrogen withdrawal activate Notch signaling. Combined inhibition of Not...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.323
更新日期:2010-01-14 00:00:00
abstract::Several small GTPases of the Ras superfamily have been shown to antagonize TGFbeta signaling in human tumor cell lines. Some of these GTPases are post-translationally modified by farnesylation, a lipid modification catalyzed by farnesyltransferase and required for the proteins to attach to membranes and to function. I...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203920
更新日期:2000-11-16 00:00:00
abstract::Replication origins are 'licensed' for a single initiation event by loading Mcm2-7 complexes during late mitosis and G1. Licensing is blocked at other cell cycle stages by the activity of cyclin-dependent kinases and a small protein called geminin. Here, we describe the effects of over-expressing a non-degradable form...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205910
更新日期:2002-09-26 00:00:00
abstract::Although it has been demonstrated that transformed progenitor cell population can contribute to tumor initiation, factors contributing to this malignant transformation are poorly known. Using in vitro and xenograft-based models, previous studies demonstrated that miR-489 acts as a tumor suppressor miRNA by targeting v...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0439-1
更新日期:2019-01-01 00:00:00
abstract::Promoter hypermethylation is an important means for the transcriptional repression of a number of cancer-associated genes. However, the underlying mechanism of this aberration in cancer remains unclear. Here, we examined 5' CpG island methylation status and expression of the p14(ARF), p16(INK4a) and RASSF1A tumor supp...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205581
更新日期:2002-07-18 00:00:00
abstract::Mxi1 is a basic region helix-loop-helix leucine zipper (bHLH/LZ) protein that, in association with Max, antagonizes Myc oncogenic activities. A possible mechanistic basis for Mxi1-mediated repression was provided by the recent demonstration that the repressive potential of Mxi1 correlates with its ability to physicall...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-03-07 00:00:00
abstract::UV irradiation of mammalian cells results in the activation of transcription factors which mediate induction of early response genes designed to repair and minimise the damage sustained by the cell. Evidence from studies in HeLa cells suggest that UVC regulates NF-kappa B activity via tyrosine kinases and activation o...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-02-15 00:00:00
abstract::Steroid receptor co-activator-3 (SRC-3/AIB1) is an oncogene that is amplified and overexpressed in many human cancers. However, the molecular mechanisms that regulate 'activated SRC-3 oncoprotein' turnover during tumorigenesis remain to be elucidated. Here, we report that speckle-type POZ protein (SPOP), a cullin 3 (C...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.151
更新日期:2011-10-20 00:00:00
abstract::We have cloned and sequenced the nov gene (novH) which is the homolog of the chicken nov proto-oncogene overexpressed in avian nephroblastomas. The novH gene is highly conserved and encodes a putative IGF-binding protein similar to that of chicken. We report that relative to autologous normal kidney expression of novH...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00