Metastatic dissemination of the primary tumor is the major cause of death in colorectal cancer (CRC) patients. Multiple chromosomal breaks and chromothripsis, a phenomenon involving multiple chromosomal fragmentations occurring in a single catastrophic event, are associated with cancer genesis, progression and developing of metastases. The aim of this study was to evaluate the effect of chromothripsis and total breakpoint count (breakpoint instability index) on progression-free survival (PFS). A total of 19 patients with metastatic CRC (mCRC) receiving FOLFOX first-line palliative chemotherapy between August, 2011 and October, 2012 were selected for this study. The results indicated that the highest breakpoint count was observed in chromosomes 1, 2 and 6. Chromothripsis was detected in 52.6% of the study patients. Furthermore, chromothripsis was associated with an increased median PFS (mPFS; 14 vs. 8 months, respectively; P=0.03), but an association with overall survival was not identified. The present study demonstrated that chromothripsis affected CRC patient survival, suggesting a role for this event as a prognostic and predictive marker in mCRC treatment.

BackgroundHereditary triple-negative breast cancer patients have better recurrence-free survival than triple-negative sporadic ones. High expression of some of the miRNAs is related to worse overall and disease-free survival of triple-negative breast cancer patients. The attempt to associate expression level of some miRNA in triple-negative hereditary and sporadic breast cancers to disease specific survival was performed in this study.Material and methodsStudy group was made of 18 triple-negative breast cancer patients harboring the BRCA1 gene mutations and 32 triple-negative sporadic breast cancer patients. Quantitative amount of mir-10b, mir-21, mir-29a, mir-31, and mir-214 by real-time PCR was assessed. The disease-specific survival in relation of high and low levels of some of the miRNAs was analyzed using Log-rank (Mantel-Cox) test.ResultsMiR-214 showed significantly higher expression level in sporadic tissues than in hereditary ones (p = 0.0005). Triple-negative breast cancer patients with high level of miR-214 showed significantly worse disease-specific survival than patients with low level (p = 0.0314).ConclusionsOur finding suggests that miR-214 possibly could be used as a potential prognostic biomarker for triple-negative breast cancer patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13053-015-0028-z) contains supplementary material, which is available to authorized users.

BackgroundThe estimated ratio of hereditary breast/ovarian cancer (HBOC) based on family history is 1.5% in Latvia. This is significantly lower than the European average of 5–10%. Molecular markers like mutations and SNPs can help distinguish HBOC patients in the sporadic breast and ovarian cancer group.Methods50 patients diagnosed with HBOC in the Latvian Cancer Registry from January 2005 to December 2008 were screened for BRCA1 founder mutation-negatives and subjected to targeted resequencing of BRCA1 and BRCA2 genes. The newly found mutations were screened for in the breast and ovarian cancer group of 1075 patients by Real Time-PCR/HRM analysis and RFLP.ResultsFour BRCA2 mutations including three novel BRCA2 frameshift mutations and one previously known BRCA2 frameshift mutation and one BRCA1 splicing mutation were identified. Two of the BRCA2 mutations were found in a group of consecutive breast cancer patients with a frequency of 0.51% and 0.38%.ConclusionsMolecular screening of sequential cancer patients is an important tool to identify HBOC families.

Introduction. Pathological complete remission of liver metastases is a rare colon cancer treatment outcome with increased 5-year survival of 76%. Case report. Metastatic colorectal cancer patient with pathological complete remission of large hepatic metastasis after palliative chemotherapy in combination with bevacizumab is presented. Solitary liver metastasis measuring 8 cm was observed in computed tomography (CT) scan before combined treatment. The best radiological response during treatment with FOLFOX-4 and bevacizumab therapy was partial remission and patient underwent partial hepatectomy. Since the operation material was free of viable adenocarcinoma cells the effect of FOLFOX-4 in combination with bevacizumab treatment was interpreted as the pathological complete remission. Conclusion. Use of combination chemotherapy and targeted therapy with the aim to reduce initially unresectable liver metastasis is the best option to achieve complete pathological remission and significantly prolong survival

Purpose The lower breast cancer incidence in Asian populations compared with Western populations has been speculated to be caused by environmental and genetic variation. Early-onset breast cancer occupies a considerable proportion of breast cancers in Asian populations, but the reason for this is unclear. We aimed to examine miRNA expression profiles in different age-onset groups and pathological subtypes in Asian breast cancer. Methods At the first stage, 10 samples (tumor: n = 6, normal tissue: n = 4) were analyzed with an Agilent microRNA 470 probe microarray. Candidate miRNAs with expression levels that were significantly altered in breast cancer samples or selected from a literature review were further validated by quantitative real-time PCR (qPCR) of 145 breast cancer samples at the second stage of the process. Correlations between clinicopathological parameters of breast cancer patients from different age groups and candidate miRNA expression were elucidated. Results In the present study, the tumor subtypes were significantly different in each age group, and an onset age below 40 had poor disease-free and overall survival rates. For all breast cancer patients, miR-335 and miR-145 were down-regulated, and miR-21, miR-200a, miR-200c, and miR-141 were up-regulated. In very young patients (age < 35 y/o), the expression of 3 and 8 specific miRNAs were up-and down-regulated, respectively. In young patients (36-40 y/o), 3 and 3 specific miRNAs were up-and down-regulated, respectively. miR-532-5p was up-regulated in triple-negative breast cancer.

Our objective was to determine: 1) whether the checkpoint kinase 2 (CHEK2) del5395 (g.27417113-27422508 del, NC_000022.11) is a founder mutation in the Latvian population, 2) if there is an association between CHEK2 del5395 mutation and cancer risk, and 3) and whether the CHEK2 del5395 mutation impacts cancer predisposition in Chernobyl disaster liquidators (the civil and military personnel who were called upon to deal with consequences of the 1986 nuclear disaster) as well as geriatric populations. We recruited 438 breast cancer patients, 568 colorectal cancer patients, 399 ovarian cancer patients, 419 prostate cancer patients, 526 healthy blood donors, 480 Chernobyl disaster liquidators and 444 geriatric cancer-free participants. DNA samples were isolated from blood samples and subjected to multiplex polymerase chain reaction (PCR). The truncation of del5395 was estimated by fragment size of the multiplex PCR.All groups were compared to the healthy blood donors using Fisher’s exact test. All p values were two-sided and the odds ratios (OR) calculated by two-by-two table. In cancer groups, the del5395 mutation was most frequently observed in the ovarian cancer group (1.00%, OR = 1.32). In control groups, the del5395 mutation was most frequent (0.76%) in the healthy donors, which exceeded its frequency in the Chernobyl liquidators group and the geriatric group by 0.01 and 0.08%, respectively. For all groups, the OR appeared to be >1 only in ovarian cancer patients. However, OR rates showed no statistical significance in either cancer or control groups, with the p value fluctuating within the range of 0.39-1.00. The CHEK2 gene del5395 is a founder mutation in the Latvian population, which, however, does not have a direct impact on genetic predisposition toward colorectal, breast, ovarian and prostate cancer.

modulate classical p53-regulated responses. Furthermore, even for wellestablished p53 targets that were differentially expressed both at transcriptional and translational levels, quantitative differences between transcriptome, subpolysomal and polysomal RNAs were evident. This observation, confirmed by qPCR assays, led us to identify processes of fine-tuning mRNA fate that we classify as translational-thrust or-drag that can act on up to 25% of the~170 known p53 target genes. Seeking mechanisms underlying gene expression uncoupling, we identified p53-dependent modulation of five RNA binding proteins where hnRNPD (AUF1) and CPEB4 are direct p53 transcriptional targets and SRSF1, DDX17, YBX1 are indirect targets modulated at translational level in a p53-directed manner. In particular, YBX1 translation appeared to be reduced by p53 via two different mechanisms, one related to mTOR inhibition and the second to miR-34a expression. Conclusions: Overall, we establish p53 as a master regulator of translational control and identify new p53 target genes affecting translation that can contribute to p53-dependent cellular responses. Based on the functions of these target genes, it becomes apparent that selectivity at the level of mRNA translation, next to transcriptional selectivity, provides an important contribution to shape p53-directed responses. No conflict of interest. 283 Disruption of cortical tension patterning drives the outgrowth of oncogenic cells

Introduction. Anaemia is a clinically important and increasingly frequent finding in cardiac surgery. Whether preoperative anaemia is an independent risk factor for adverse outcomes after elective cardiac surgery is still under discussion. We analysed prevalence of preoperative anaemia and its influence to outcome in patients undergoing elective on-pump cardiac surgery. Aim of the Study. To analyse preoperative anaemia and its influence to outcome in patients undergoing elective cardiac surgery. Material and Methods. Prospective study was done from October 2013 to January 2014 at the Cardiac Surgery Centre of Pauls Stradins Clinical University Hospital. Data were collected on 192 patients who underwent elective on-pump cardiac surgery. The prevalence of preoperative anaemia was defined as haemoglobin (Hb) for men < 130 g/l, for women < 120 g/l. Surgical bleeding was found for 17 patients during re-operation, those were excluded from future analysis. Consequently, 175 were divided into two groups: anaemic (n=69) and control group (n=106). Anaemia relationships with haemotransfusions, postoperative complications as acute heart failure, infections, atrial fibrillation, acute kidney injury (AKI) and length of mechanical ventilation and stay in hospital were obtained. Results. The overall prevalence of preoperative anaemia was 39%. Preoperative Hb values were 111 ± 13 g/l, MCHC 329 ± 12 g/l, MCV 86 ± 8 fl in anaemic group and in a control group Hb 140 ± 11 g/l, MCHC 335 ± 8 g/l, MCV 89 ± 9 fl (p < 0,001; p < 0,001; p = 0,01). Anaemic patients in 80% received red blood cell (RBC) transfusions 586 ± 801 ml and 47% in control group, p < 0,0001. Fresh frozen plasma (FFP) and Cryoprecipitate (Cryo) transfused volumes did not differ statistically between groups (p = 0,15; p = 0,2). Sensitivity and specificity of preoperative anaemia to haemotransfusions: area under curve for RBC transfusions 0,71, for FFP 0,57, for Cryo 0,44. Hb levels before and 24 hours after surgery correlated with RBC transfusions (r =-0,4,-0,5; p < 0,001). Anaemia is an independent risk factor for postoperative infection (p=0.04; OR 4.2; 95% C.I. 1.2-16.7) and AKI (p=0,02; OR 2.3; 95% C.I. 1.1-4.6). RBC transfusion volume is adjusted to postoperative infections and AKI, respectively, p = 0.004 and p = 0.01. Anaemic patients had statistically longer mechanical lung ventilation (p = 0.02) and stay in hospital (p = 0.04). Conclusions. Preoperative anaemia, mainly normocytic normochromic (72%) and microcytic hypochromic (13%), is observed in 39%. Anaemic patients received major RBC transfusions to compare with non-anaemic patients. Preoperative anaemia and volume of RBC transfused are associated with development of AKI and infections postoperatively. Preoperative anaemia prolongs mechanical lung ventilation and in-hospital stay.