排序方式: 共有17条查询结果,搜索用时 15 毫秒
11.
Quesada V Conde L Villamor N Ordóñez GR Jares P Bassaganyas L Ramsay AJ Beà S Pinyol M Martínez-Trillos A López-Guerra M Colomer D Navarro A Baumann T Aymerich M Rozman M Delgado J Giné E Hernández JM González-Díaz M Puente DA Velasco G Freije JM Tubío JM Royo R Gelpí JL Orozco M Pisano DG Zamora J Vázquez M Valencia A Himmelbauer H Bayés M Heath S Gut M Gut I Estivill X López-Guillermo A Puente XS Campo E López-Otín C 《Nature genetics》2012,44(1):47-52
Here we perform whole-exome sequencing of samples from 105 individuals with chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults in Western countries. We found 1,246 somatic mutations potentially affecting gene function and identified 78 genes with predicted functional alterations in more than one tumor sample. Among these genes, SF3B1, encoding a subunit of the spliceosomal U2 small nuclear ribonucleoprotein (snRNP), is somatically mutated in 9.7% of affected individuals. Further analysis in 279 individuals with CLL showed that SF3B1 mutations were associated with faster disease progression and poor overall survival. This work provides the first comprehensive catalog of somatic mutations in CLL with relevant clinical correlates and defines a large set of new genes that may drive the development of this common form of leukemia. The results reinforce the idea that targeting several well-known genetic pathways, including mRNA splicing, could be useful in the treatment of CLL and other malignancies. 相似文献
12.
Loveday C Turnbull C Ramsay E Hughes D Ruark E Frankum JR Bowden G Kalmyrzaev B Warren-Perry M Snape K Adlard JW Barwell J Berg J Brady AF Brewer C Brice G Chapman C Cook J Davidson R Donaldson A Douglas F Greenhalgh L Henderson A Izatt L Kumar A Lalloo F Miedzybrodzka Z Morrison PJ Paterson J Porteous M Rogers MT Shanley S Walker L;Breast Cancer Susceptibility Collaboration 《Nature genetics》2011,43(9):879-882
Recently, RAD51C mutations were identified in families with breast and ovarian cancer. This observation prompted us to investigate the role of RAD51D in cancer susceptibility. We identified eight inactivating RAD51D mutations in unrelated individuals from 911 breast-ovarian cancer families compared with one inactivating mutation identified in 1,060 controls (P = 0.01). The association found here was principally with ovarian cancer, with three mutations identified in the 59 pedigrees with three or more individuals with ovarian cancer (P = 0.0005). The relative risk of ovarian cancer for RAD51D mutation carriers was estimated to be 6.30 (95% CI 2.86-13.85, P = 4.8 × 10(-6)). By contrast, we estimated the relative risk of breast cancer to be 1.32 (95% CI 0.59-2.96, P = 0.50). These data indicate that RAD51D mutation testing may have clinical utility in individuals with ovarian cancer and their families. Moreover, we show that cells deficient in RAD51D are sensitive to treatment with a PARP inhibitor, suggesting a possible therapeutic approach for cancers arising in RAD51D mutation carriers. 相似文献
13.
INTERMEDIUM-C, a modifier of lateral spikelet fertility in barley, is an ortholog of the maize domestication gene TEOSINTE BRANCHED 1 总被引:1,自引:0,他引:1
Ramsay L Comadran J Druka A Marshall DF Thomas WT Macaulay M MacKenzie K Simpson C Fuller J Bonar N Hayes PM Lundqvist U Franckowiak JD Close TJ Muehlbauer GJ Waugh R 《Nature genetics》2011,43(2):169-172
The domestication of cereals has involved common changes in morphological features, such as seed size, seed retention and modification of vegetative and inflorescence architecture that ultimately contributed to an increase in harvested yield. In barley, this process has resulted in two different cultivated types, two-rowed and six-rowed forms, both derived from the wild two-rowed ancestor, with archaeo-botanical evidence indicating the origin of six-rowed barley early in the domestication of the species, some 8,600-8,000 years ago. Variation at SIX-ROWED SPIKE 1 (VRS1) is sufficient to control this phenotype. However, phenotypes imposed by VRS1 alleles are modified by alleles at the INTERMEDIUM-C (INT-C) locus. Here we show that INT-C is an ortholog of the maize domestication gene TEOSINTE BRANCHED 1 (TB1) and identify 17 coding mutations in barley TB1 correlated with lateral spikelet fertility phenotypes. 相似文献
14.
Amplification and enhanced expression of the c-myc oncogene in mouse SEWA tumour cells 总被引:2,自引:0,他引:2
M Schwab G Ramsay K Alitalo H E Varmus J M Bishop T Martinsson G Levan A Levan 《Nature》1985,315(6017):345-347
SEWA tumour cells are derived from an osteosarcoma induced in an A.SW mouse by infection with polyoma virus. Cytogenetic analyses have revealed three different characteristic chromosomal abnormalities diagnostic for the presence of amplified genes: 'double minutes' (DMs), homogeneously staining chromosomal regions (HSRs) and C-bandless chromosomes (CMs; for review see ref. 2). DMs may undergo fluctuation in number depending on the conditions in which the cells grow. Their number usually increases after injection of cells into a mouse and often is reduced to undetectable levels when the cells are explanted back into tissue culture; when the cells are re-introduced into the mouse, they again acquire multiple DMs. We show here that cells of SEWA lines carrying DMs, HSRs or CMs contain amplified copies of the proto-oncogene c-myc and enhanced levels of c-myc messenger RNA and c-myc protein. DMs or CMs are the sites of c-myc amplification in two different SEWA lines. 相似文献
15.
The activity of the ouabain-sensitive Na, K ATPase was measured in membrane fractions of the submandibular gland of 1-, 7-, 14- and 21-day-old rats. This activity increased with age and reached adult levels by 21 days. 相似文献
16.
Summary The activity of the ouabain-sensitive Na, K ATPase was measured in membrane fractions of the submandibular gland of 1-, 7-, 14- and 21-day-old rats. This activity increased with age and reached adult levels by 21 days. 相似文献
17.
The myelocytomatosis viruses are a family of replication-defective avian retroviruses that cause a variety of tumours in chickens and transform both fibroblasts and macrophages in culture through the activity of their oncogene v-myc. A closely related gene (c-myc) is found in vertebrate animals and is thought to be the progenitor of v-myc. Changes in the expression and perhaps the structure of c-myc have been implicated in the genesis of avian, murine and human tumours (for a review, see ref. 15). Elucidation of the mechanisms by which v-myc and c-myc might elicit tumorigenesis requires identification of the proteins encoded by these genes. To this end, we have expressed a portion of v-myc in a bacterial host and used the resulting protein to raise antisera that react with myc proteins. We report here that v-myc and c-myc encode closely related proteins with molecular weights (MWs) of approximately 58,000. Integration of retroviral DNA near or within c-myc in avian lymphomas apparently enhances expression of the gene. Here we have used cells from one such tumour to identify the protein encoded by c-myc and find that the coding domain for the gene is probably intact. 相似文献