| 31. |
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| 32. |
- Hicks, J, et al.
(författare)
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Novel patterns of genome rearrangement and their association with survival in breast cancer
- 2006
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1088-9051. ; 16:12, s. 1465-1479
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Tidskriftsartikel (refereegranskat)abstract
- Representational Oligonucleotide Microarray Analysis (ROMA) detects genomic amplifications and deletions with boundaries defined at a resolution of ∼50 kb. We have used this technique to examine 243 breast tumors from two separate studies for which detailed clinical data were available. The very high resolution of this technology has enabled us to identify three characteristic patterns of genomic copy number variation in diploid tumors and to measure correlations with patient survival. One of these patterns is characterized by multiple closely spaced amplicons, or “firestorms,” limited to single chromosome arms. These multiple amplifications are highly correlated with aggressive disease and poor survival even when the rest of the genome is relatively quiet. Analysis of a selected subset of clinical material suggests that a simple genomic calculation, based on the number and proximity of genomic alterations, correlates with life-table estimates of the probability of overall survival in patients with primary breast cancer. Based on this sample, we generate the working hypothesis that copy number profiling might provide information useful in making clinical decisions, especially regarding the use or not of systemic therapies (hormonal therapy, chemotherapy), in the management of operable primary breast cancer with ostensibly good prognosis, for example, small, node-negative, hormone-receptor-positive diploid cases.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Hammarstedt, Lilian, et al.
(författare)
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Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer
- 2006
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Ingår i: Int J Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 119:11, s. 2620-3
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Tidskriftsartikel (refereegranskat)abstract
- Smoking and alcohol are well-known etiological factors in tonsillar cancer. However, as in cervical cancer, human papillomavirus (HPV) is currently found in a sizable proportion of tonsillar cancer. Recent reports from the U.S. and Finland show an increase in the incidence of tonsillar cancer, without a parallel rise in smoking and alcohol consumption. This study investigates whether the incidence of tonsillar cancer has also changed in Sweden and whether a possible explanation of the increase is a higher proportion of HPV-positive tonsillar cancer. The incidence of tonsillar cancer between 1970 and 2002 in the Stockholm area was obtained from the Swedish Cancer Registry. In parallel, 203 pretreatment paraffin-embedded tonsillar cancer biopsies taken during 1970-2002 from patients in the Stockholm area were tested for presence of HPV DNA by PCR. The incidence of tonsillar cancer increased 2.8-fold (2.6 in men and 3.5 in women) from 1970 to 2002. During the same period, a significant increase in the proportion of HPV-positive tonsillar cancer cases was observed, as it increased 2.9-fold (p < 0.001). The distribution of HPV-positive cases was 7/30 (23.3%) in the 1970s, 12/42 (29%) in the 1980s, 48/84 (57%) in the 1990s and 32/47 (68%) during 2000-2002. We have demonstrated a highly significant and parallel increase both in the incidence of tonsillar cancer and the proportion of HPV-positive tumors. Hence, HPV may play an important role for the increased incidence of tonsillar cancer. This should definitely influence future preventive strategies as well as treatment for this type of cancer.
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| 37. |
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| 38. |
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| 39. |
- Jang, Sung-Wuk, et al.
(författare)
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Serine/arginine protein-specific kinase 2 promotes leukemia cell proliferation by phosphorylating acinus and regulating cyclin A1
- 2008
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Ingår i: Cancer Research. - 1538-7445 .- 0008-5472. ; 68:12, s. 4559-4570
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Tidskriftsartikel (refereegranskat)abstract
- Serine/arginine (SR) protein-specific kinase (SRPK), a family of cell cycle-regulated protein kinases, phosphorylate SR domain-containing proteins in nuclear speckles and mediate the pre-mRNA splicing. However, the physiologic roles of this event in cell cycle are incompletely understood. Here, we show that SRPK2 binds and phosphorylates acinus, an SR protein essential for RNA splicing, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin A1 but not A2 up-regulation. Acinus S422D, an SRPK2 phosphorylation mimetic, enhances cyclin A1 transcription, whereas acinus S422A, an unphosphorylatable mutant, blocks the stimulatory effect of SRPK2. Ablation of acinus or SRPK2 abrogates cyclin A1 expression in leukemia cells and arrest cells at G, phase. Overexpression of acinus or SRPK2 increases leukemia cell proliferation. Furthermore, both SRPK2 and acinus are overexpressed in some human acute myelogenous leukemia patients and correlate with elevated cyclin A1 expression levels, fitting with the oncogenic activity of cyclin A1 in leukemia. Thus, our findings establish a molecular mechanism by which SR splicing machinery regulates cell cycle and contributes to leukemia tumorigenesis.
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| 40. |
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