生物信息学分析实验报告

1、分别写出2010年以来，国际上与Ovarian cancer、Breast cancer、Leukemia相关的文献有多少篇？写出3篇研究性论文标题和摘要，写出5篇综述性论文标题和摘要；数据库：科学引文索引数据库(SCI：Science Citation Index)与Ovarian cancer相关的文献有11,303篇与Breast cancer相关的文献有56,209篇与Leukemia相关的文献有32,912篇综述性论文标题和摘要1.Hemochromatosis and ovarian cancer摘要:Evaluation of: Gannon PO, Medelci S, Le Page C et al. Impact of hemochromatosis gene (HFE) mutations on epithelial ovarian cancer risk and prognosis. Int. J. Cancer 128(10), 2326-2334 (2011). The frequency of two mutations (C282Y and D62H) of the hemochromatosis gene were investigated in women with ovarian cancer. A single allele mutation of the C282Y but not the H63D gene product was detected in 8-9% of women with benign ovarian tumors (n = 124) and ovarian cancers (n = 360) compared with 2.5% for controls (n = 80) representing a 4.9-fold increase in risk.With high-grade serous ovarian cancers (n = 179), the survival rate of women with a single allele C282Y mutation was reduced from 39 to 19 months. These results implicate mutations of the hemochromatosis gene in the generation and severity of ovarian cancers, which may have prognostic value.2.Differences between women who pursued genetic testing for hereditary breastand ovarian cancer and their at-risk relatives who did not.摘要: Purpose/Objectives: To (a) examine differences in appraisals of hereditary breast and ovarian cancer (HBOC), psychological distress, family environment, and decisional conflict between women who pursued genetic testing and their at-risk relatives who did not, and (b) examine correlations among appraisals of HBOC, psychological distress, family environment, and decisional conflict regarding genetic testing in these two cohorts of women.Design: Descriptive, cross-sectional cohort study.Setting: Two clinics affiliated with a major research university in the midwestern United States.Sample: 372 women aged 18 years and older. 200 pursued genetic testing for BRCA1 and BRCA2 mutations (probands) and 172 of their female relatives who had a greater than 10% prior probability of being a mutation carrier but had not pursued testing.Methods: After providing informed consent, probands and relatives were mailed self-administered questionnaires.Main Research Variables: Perceived risk, knowledge of HBOC risk factors and modes of gene inheritance, perceived severity, perceived controllability, psychological distress, family relationships, family communication, and decisional conflict about genetic testing.Findings: T tests revealed that probands perceived higher risk and had more psychological distress associated with breast cancer.Probands had more knowledge regarding risk factors and gene inheritance, and greater decisional conflict regarding genetic testing. Relatives reported higher perceived severity and controllability.No differences were observed in family relationships and family communication between probandsand relatives. Pearson correlations revealed different patterns in knowledge, perceived controllability, family relationships, and decisional conflict between probands and relatives.Conclusions: Significant differences exist between women who pursue genetic testing and those who do not. The family environment influences adjustment to HBOC and decisions about genetic testing.Implications for Nursing: Enhancing the family communication process about HBOC can provide informational and emotional support to high-risk women and promote decision making about genetic testing.3.Incidence and mortality in epithelial ovarian cancer by family history of anycancer摘要: Practically all data on familial risk in ovarian and other cancers are based on incident cancer, whereas familiality in cancer mortality is largely unknown. If fatal forms of cancer are a highly familial subtype, then familial risk for mortality may exceed that of incidence, which is relevant for clinical decision making and counseling. Ovarian cancer patients in the nationwide Swedish Family Cancer Database were classified according to fatal and nonfatal (incident) family history. Familial risks for incident and fatal ovarian cancer were calculated for offspring based on their parental or sibling family history of any cancer using standardized incidence ratios (SIRs) for incidence and standardized mortality ratios (SMRs) for mortality. Offspring without family history were referents. The database included 24,757 mothers and 8138 daughters with ovarian cancer. When a mother had ovarian cancer, the SIR for incident ovarian cancer in daughters was 2.69, and when a sister had ovarian cancer it was 3.49. The SMRs for fatal cancer by fatal cancer in probands were 3.39 and 5.80, respectively. For fatal serous cancers among siblings, the SMR was 6.16, compared with 10.01 for the endometrioid type. Ovarian cancer was associated with maternal (SIR, 1.22; SMR, 1.56) and sororal breast cancer (SIR, 1.27). Another discordant association was between ovarian and paternal prostate cancer (SIR, 1.12; SMR, 1.66). Fatal familial risks were higher for concordant ovarian, ovarian-breast, and ovarian-prostate cancers than the corresponding incident risks. This may suggest that highly fatal subtypes exist for these cancers, calling for genetic dissection. Cancer 2011. 2011 American Cancer Society. Copyright 2011 American Cancer Society.4.Knock-down of amphiregulin inhibits cellular invasion in inflammatory breastcancer.摘要: We have previously shown that SUM-149 human breast cancer cells require an amphiregulin (AREG) autocrine loop for cell proliferation. We also demonstrated that AREG can increase epidermal growth factor receptor (EGFR) stability and promote EGFR localization to the plasma membrane. In the present studies we successfully knocked-down AREG expression in SUM-149 cells by lentiviral infection of AREG shRNA. In the absence of AREG expression, SUM-149 cell growth was slowed, but not completely inhibited. Furthermore, cells infected with AREG shRNA constructs showed an increase in EGFR protein expression by Western blot. Immunofluorescence and confocal microscopy showed that following AREG knock-down, EGFR continued to localize to the cell surface. Soft agar assays demonstrated that AREG knock-down cells retain anchorage-independent growth capacity. Additionally mammosphere forming assays and Adefluor staining analysis showed that knock-down of AREG expression did not affect the expression of stem cell phenotypes. However, following AREG knock-down, SUM-149 cells demonstrated a dramatic decrease in their ability to invade a Matrigel matrix. Consistent with this observation,microarray analysis comparing cells infected with a non-silencing vector to the AREG knock-down cells, identified genes associated with the invasive phenotype such as RHOB and DKK1, and networks associated with cell motility such as integrin-linked kinase signaling, and focal adhesion kinase signaling. AREG was also found to modulate WNT and Notch signaling in these cells. Thus, AREG functions in regulating the invasive phenotype, and we propose that this regulation may be through altered signaling that occurs when AREG activates plasma membrane localized EGFR. J.Cell. Physiol. 226: 2691-2701, 2011. 2011 Wiley-Liss, Inc. Copyright 2011 Wiley-Liss, Inc.5.Prognostic impact of c-KIT mutations in core binding factor acute myeloidleukemia.摘要: This study sought to define the prognostic impact of c-KIT mutations in core binding factor acute myeloid leukemia (CBF AML) patients. A total of 116 patients diagnosed as CBF AML in Asan Medical Center from January 1999 to May 2010 were enrolled in this study. We applied melting curve analyses and direct sequencing methods to confirm c-KIT mutations in exon 17 (mutKIT17) and exon 8 (mutKIT8). Of the total 116 patients, mutKIT17 were found in 36 (31%) and mutKIT8 were found in 7 (6%). In patients with t(8;21), prognosis was significantly poorer in those with mutKIT17 compared to those without the mutation. This difference was limited to adults. In patients with inv(16), there was no prognostic impact of c-KIT mutations. Therefore, an analysis of mutKIT17 in adult CBF AML patients with t(8;21) is recommended as a means to predict prognosis. Copyright 2011 Elsevier Ltd. All rights reserved.研究性论文标题和摘要1. Prolactin increases survival and migration of ovarian cancer cells: Importance ofprolactin receptor type and therapeutic potential of S179D and G129R receptor antagonists.摘要: Variably-spliced prolactin receptors (PRLRs) and PRL are expressed by the ovarian cancer cell lines, TOV-112D, OV-90 and TOV-21G. Incubation in the PRLR antagonists, G129R- or S179D-PRL, or anti-PRL reduced cell number, indicating a functional autocrine PRL growth loop. Added PRL promoted, and the antagonists decreased, cell migration. When cells were stressed, added PRL decreased apoptosis and increased survival, and the antagonists had the opposite effect. Cells expressing higher long:short PRLR ratios had increased growth, survival and migration in response to PRL. Results suggest that PRLR antagonists may be therapeutically beneficial in ovarian cancer. Copyright 2011 Elsevier Ireland Ltd. All rights reserved2. (R)-FTY720 methyl ether is a specific sphingosine kinase 2 inhibitor: Effect onsphingosine kinase 2 expression in HEK 293 cells and actin rearrangement and survival of MCF-7 breast cancer cells摘要:Sphingosine kinase 2 (SK2) catalyses the conversion of sphingosine to the bioactive lipid sphingosine 1-phosphate (Si P). We report here, the stereospecific synthesis of an analogue of FTY720 called (R)-FTY720-OMe, which we show is a competitive inhibitor of SK2. (R)-FTY720-OMe failed to inhibit sphingosine kinase 1 activity, thereby demonstrating specificity for SK2. Prolonged treatment of HEK 293 cells with (R)-FTY720-OMe also induced a reduction in SK2 expression. In addition. (R)-FTY720-OMe inhibited DNA synthesis and prevented S1P-stimulated rearrangement of actin in MCF-7 breast cancer cells. These findings demonstrate that SK2 functions as a pro-survival protein and is involved in promoting actin rearrangement into membrane ruffles/lamellipodia inresponse to SIP in MCF-7 breast cancer cells. (C) 2011 Elsevier Inc. All rights reserved3.The BH3-only protein Noxa is stimulated during apoptosis of chronic lymphocyticleukemia cells triggered by M2YN, a new plant-derived extract.摘要:Deficiency of apoptosis is a hallmark of chronic lymphocytic leukemia (CLL) cells. M2Yn is a natural extract from plants of central Asia, identified for its antiangiogenic properties and its ability to block the migration of malignant cells. Here, we report that in vitro treatment of cells derived from CLL patients with M2Yn results in internucleosomal DNA fragmentation, phosphatidylserine externalization, mitochondrial membrane depolarization, caspase-3 activation and cleavage of the caspase substrate PARP-1. The extents of these effects depend on the patients and are mostly comparable to those of flavopiridol or hyperforin, two known plant-derived apoptosis inducers of CLL cells. M2Yn does not modulate Mcl-1 expression, while downregulation of this antiapoptotic protein is involved in the action of flavopiridol. By contrast, M2Yn, like hyperforin, upregulates the Noxa protein, possibly by inhibiting proteasomal activity. This BH3-only protein is known to trigger the activation of the pro-apoptotic protein Bak through displacement of the Mcl-1/Bak complex at the mitochondrial membrane, as actually observed here in M2Yn-treated cells. Our data, therefore, show that M2Yn can induce the caspase-dependent mitochondrial pathway of apoptosis in CLL cells via a mechanism resembling that of hyperforin. Our data also confirm that the BH3-only protein Noxa is a relevant target for CLL therapy.2、请以”P53”、”BRCA1”、”BRCA2”、”RAD51D”、”MSH6”、”MLH1”为关键词，在NCBI的网站上搜索人的序列，要求列出下列信息：物种的拉丁文、序列的ACCNUM和碱基序列，并找出这些基因在酵母、果蝇和小鼠中的同源基因，列出物种的拉丁文，序列的ACCNUM；（Saccharomyces cerevisiae，Drosophila melanogaster，Mus Musculus）P53：Homo sapiensNC_000017.10Chromosome: 17; NC_000017.10 (7571720..7590863, complement)与Saccharomyces cerevisiae同源基因为BK006938.2与Drosophila melanogaster同源基因为BT021431.1与Mus Musculus同源基因为AK156276.1BRCA1：Homo sapiensNC_000017.10Chromosome: 17; NC_000017.10 (41196312..41277500, complement)与Saccharomyces cerevisiae同源基因为BK006949.2与Drosophila melanogaster同源基因为AE014134.5与Mus Musculus同源基因为AL590996.12BRCA2：Homo sapiensNC_000013.10Chromosome: 13; NC_000013.10 (32889617..32973809)与Saccharomyces cerevisiae同源基因为BK006939与Drosophila melanogaster同源基因为AE014134与Mus Musculus同源基因为AC154885RAD51D：Homo sapiensNC_000017.10Chromosome: 17; NC_000017.10 (33426811..33446888, complement)与Saccharomyces cerevisiae同源基因为S66120与Drosophila melanogaster同源基因为AE014298与Mus Musculus同源基因为AK011387MSH6：Homo sapiensNC_000002.11Chromosome: 2; NC_000002.11 (48010221..48034092)与Saccharomyces cerevisiae同源基因为BK006942与Drosophila melanogaster同源基因为BT050543与Mus Musculus同源基因为AC087233MLH1：Homo sapiensNC_000003.11Chromosome: 3; NC_000003.11 (37034841..37092337)与Saccharomyces cerevisiae同源基因为BK006940与Drosophila melanogaster同源基因为AE013599与Mus Musculus同源基因为AK1710523、请分别用核酸-核酸、核酸-蛋白质的blast方法，分析以下这个序列可能是一个什么样的序列，要求列出：blast程序、比对的数据库、相似性最高的序列的ACCNUM、相似性最高序列所在的物种和相似性最高的序列的功能描述；核酸-核酸blast程序: BLASTN 2.2.25比对的数据库: nr/nt相似性最高的序列的ACCNUM: U01876.1 GI:3478631相似性最高序列所在的物种: Deinococcus radiodurans R1相似性最高的序列的功能描述:RecA is a bacterial enzyme which has roles inhomologous recombination, DNA repair, and the induction of the SOS response. RecA couples ATP hydrolysis to DNA strand exchange;核酸-蛋白质blast程序: BLASTX 2.2.25比对的数据库: nr相似性最高的序列的ACCNUM: NP_296061.1 GI:15807331相似性最高序列所在的物种: Deinococcus radiodurans R1相似性最高的序列的功能描述: RecA is a bacterial enzyme which has roles inhomologous recombination, DNA repair, and the induction of the SOS response. RecA couples ATP hydrolysis to DNA strand exchange;4、请分别在人类基因组数据库中找出以下基因”P53”、” BRCA1”、”BRCA2”、”RAD51D”、”MSH6”、”MLH1”的cDNA的序列，要求列出：外显子序列的起始边界，外显子基本的功能描述；P53外显子序列的起始边界(1,10927,11143,11274,12310,12575,13256,13709,13938,16831,17856)外显子基本的功能描述tumor protein p53, transcript variant 2BRCA1外显子序列的起始边界(1,1369,9705,18951,20528,21223,25604,28195,29562,30624,34452,42909,48870,50963,54246,5 7789,61533,62111,68349,74367,76290,77781,79682)外显子基本的功能描述breast cancer 1, early onset, transcript variant1BRCA2外显子序列的起始边界(1,943,3598,9597,10622,10763,11020,13964,15440,16793,20786,29079,31348,39382,40949,4226 3,47044,47700,54923,55477,61191, 63838,64271,64528,79210, 81419,82683)外显子基本的功能描述breast cancer 2, early onsetRAD51D外显子序列的起始边界(1,698,13389,16326, 16546,18505,18834)外显子基本的功能描述RAD51 homolog D (S. cerevisiae), transcript variant 4MSH6外显子序列的起始边界(1,7846,12813,15530,20339,21829,22537,23123,23371,23698)外显子基本的功能描述mutS homolog 6 (E. coli)MLH1外显子序列的起始边界(1,3270,7606,11052,13642,15465,18471,18662,21083,24157,26961,32288,35435,46837,48919,54 170, 55168,55555,57137)外显子基本的功能描述mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli), transcript variant 15、请分别获取以下人类基因”P53”、”BRCA1”、”BRCA2”、”RAD51D”、”MSH6”、”MLH1”的蛋白质序列，要求列出：氨基酸序列、蛋白质的序列号。