The genetics behind the progression of myelodysplasia to secondary acute myeloid leukemia (sAML) is poorly understood. In this study, we profiled somatic mutations and their dynamics using next generation sequencing on serial samples from a total of 124 patients, consisting of a 31 patient discovery cohort and 93 patients from two validation cohorts. Whole-exome analysis on the discovery cohort revealed that 29 of 31 patients carry mutations related to at least one of eight commonly mutated pathways in AML. Mutations in genes related to DNA methylation and splicing machinery were found in T-cell samples, which expand at the initial diagnosis of the myelodysplasia, suggesting their importance as early disease events. On the other hand, somatic variants associated with signaling pathways arise or their allelic burdens expand significantly during progression. Our results indicate a strong association between mutations in activated signaling pathways and sAML progression. Overall, we demonstrate that distinct categories of genetic lesions play roles at different stages of sAML in a generally fixed order.

BackgroundClass III β-tubulin (TUBB3) is a prognostic marker in various tumors, but the role of TUBB3 in advanced gastric cancer is not clearly defined. We analyzed the significance of TUBB3 expression, along with that of excision repair cross-complementation group 1 (ERCC1) in recurrent and metastatic gastric cancer patients receiving taxane-based first-line palliative chemotherapy.MethodsWe reviewed the cases of 146 patients with advanced gastric adenocarcinoma who received taxane-based first-line palliative chemotherapy between 2004 and 2010 at Chonnam National University Hwasun Hospital (Gwangju, Korea). Immunohistochemical staining for TUBB3 and ERCC1 was performed using paraffin wax-embedded tumor tissues. We evaluated the patients’ response to chemotherapy, progression-free survival (PFS), and overall survival (OS).ResultsIn total, 146 patients with advanced gastric cancer received docetaxel and cisplatin (n = 15) or paclitaxel and cisplatin (n = 131). The median PFS was significantly shorter for patients with high-level TUBB3 expression than for patients with low-level TUBB3 expression (3.63 vs. 6.67 months, P = 0.001). OS was not associated with TUBB3 expression (13.1 vs. 13.1 months, P = 0.769). By multivariate analysis, only TUBB3 was related to a shorter PFS (HR 2.74, 95% CI 1.91-3.91, P = 0.001). Patients with high-level ERCC1 expression showed a lower response rate than patients with low-level ERCC1 expression (24 vs. 63.2%, P = 0.001); however, ERCC1 had no clinical effect on PFS or OS.ConclusionsTUBB3 was a strong predictive marker in recurrent and metastatic gastric cancer patients receiving taxane-based first-line palliative chemotherapy. No clinical impact of ERCC1 was evident in this setting.

This study evaluated the efficacy of percutaneous radiofrequency ablation (RFA) for the treatment of metachronous liver metastases of gastric cancer. We enrolled a total of 44 patients who underwent percutaneous RFA for the treatment of metachronous liver metastases after resection of a primary gastric adenocarcinoma from January 2002 to November 2011. The primary endpoint of this study was overall survival (OS) and recurrence-free survival (RFS) after RFA. Systemic chemotherapy was combined with RFA in 40 patients; the OS and RFS of the patients with liver-only metastasis who underwent RFA and chemotherapy were 20.9 months (95 % CI 18.4–23.4) and 9.8 months (95 % CI 9.2–10.5), respectively. On multivariate analysis, the factors independently, negatively associated with OS were extrahepatic metastatic lesions (HR 12.6, 95 % CI 3.7–42.9; p = 0.001), no chemotherapy (HR 43.3, 95 % CI 7.4–251.3; p = 0.001), and tumor number ≥2 (HR 2.6, 95 % CI 1.2–5.9; p = 0.015). The factors independently, negatively associated with RFS were extrahepatic metastatic lesions (HR 3.6, 95 % CI 1.6–7.8; p = 0.003) and bilobar intrahepatic distribution (HR 3.9, 95 % CI 1.5–9.9; p = 0.001). The efficacy of percutaneous RFA for metachronous liver metastases of gastric cancer is limited to patients with a single, unilobar metastasis without extrahepatic metastatic lesions. Combined systemic chemotherapy is very important for the prolongation of OS.

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BackgroundThe platelet–lymphocyte ratio (PLR) and neutrophil–lymphocyte ratio (NLR) have been reported as prognostic factors in various cancers, but their roles in metastatic renal cell cancer (mRCC) remain unclear. We investigated the significance of PLR and NLR, along with that of established prognostic factors, in mRCC patients receiving first-line tyrosine kinase inhibitors (TKI).MethodsData obtained from 63 mRCC patients who received first-line TKI between 2007 and 2013 were evaluated retrospectively. The association of PLR, NLR, and established prognostic factors with progression-free survival (PFS) and overall survival (OS) was analyzed using the Kaplan–Meier method. The influence of independent prognostic factors on survival was determined using multivariable Cox regression analysis.ResultsHigh NLR (>3.6) and PLR (>150) were related to shorter PFS (p = 0.001) and OS (p = 0.001). The presence of brain metastases [hazard ratio (HR) 4.94, 95% CI 1.75–13.9; p = 0.002] and high PLR (>150, HR 13.1, 95% CI 5.14–33.2; p = 0.001) were independently associated with PFS, and Eastern Cooperative Oncology Group Performance status ≥2 (HR 3.60, 95% CI 1.39–9.31; p = 0.008), lymph node metastasis (HR 2.76, 95% CI 1.11–6.86; p = 0.029), brain metastasis (HR 9.39, 95% CI 2.74–32.1; p = 0.001), and high PLR (>150, HR 16.1, 95% CI 4.41–58.4; p = 0.001) with OS.ConclusionsHigh PLR was associated with shorter survival of mRCC patients receiving first-line TKI. The PLR may be an effective independent prognostic factor in this setting.