Hepatoblastoma (HB) is the most common pediatric liver malignancy; however, hereditary predisposition and acquired molecular aberrations related to HB clinicopathological diversity are not well understood. Here, we perform an integrative genomic profiling of 163 pediatric liver tumors (154 HBs and nine hepatocellular carcinomas) based on the data acquired from a cohort study (JPLT-2). The total number of somatic mutations is precious low (0.52/Mb on exonic regions) but correlated with age at diagnosis. Telomerase reverse transcriptase (TERT) promoter mutations are prevalent in the tween HBs, selective in the transitional liver cell tumor (TLCT, > 8 years old). DNA methylation profiling reveals that classical HBs are characterized by the specific hypomethylated enhancers, which are enriched with binding sites for ASCL2, a regulatory transcription factor for definitive endoderm in Wnt-pathway. Prolonged upregulation of ASCL2, as well as fetal-liver-like methylation patterns of IGF2 promoters, suggests their “cell of origin” derived from the premature hepatoblast, similar to intestinal epithelial cells, which are highly proliferative. Systematic molecular profiling of HB is a promising approach for understanding the epigenetic drivers of hepatoblast carcinogenesis and deriving clues for risk stratification.

We can detect MYCN amplification of tumor tissue noninvasively and quantitatively by measuring the MYCN copy number in blood plasma. Determination of MYCN copy number in plasma may be useful when evaluating surgery and neoadjuvant chemotherapy.

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Single-cell sequencing of circulating tumor cells can precisely represent tumor heterogeneity and provide useful information for cancer treatment and research. After spiking TGW neuroblastoma cells into blood derived from healthy volunteer, the cells were isolated by fluorescence-activated cell sorting. DNA and mRNA were amplified by four different whole-genome amplifications (WGA) and three whole-transcriptome amplifications (WTA) methods, followed by single-cell DNA and RNA sequencing. Multiple displacement amplification (MDA)-based WGA methods showed higher amplification efficiency than other methods with a comparable depth of coverage as the bulk sample. The uniformity of coverage greatly differed among samples (12.5–89.2%), with some samples evaluated by the MDA-based WGA method using phi29 DNA polymerase and random primers showing a high (> 80%) uniformity of coverage. The MDA-based WTA method less effectively amplified mRNA and showed non-specific gene expression patterns. The PCR-based WTA using template switching with locked nucleic acid technology accurately amplified mRNA from a single cell. Taken together, our results present a more reliable and adaptable approach for CTC profiling at the single-cell level. Such molecular information on CTCs derived from clinical patients will promote cancer treatment and research.

Objective: Reportedly, fibroblast growth factor receptor 3 (FGFR3) that regulates embryonic growth and development may function as an oncoprotein in certain malignancies. We aimed to investigate the biological significance of FGFR3 expression in invasive breast cancer. Methods: FGFR3 expression was investigated in 50 invasive breast cancer specimens by immunohistochemistry. The association between FGFR3 expression and clinicopathological/molecular parameters or prognosis was evaluated. Results: Weak FGFR3 expression was observed in myoepithelial cells, but not in duct epithelial cells, of the normal mammary ducts and lobules. FGFR3 expression in breast cancer cells was observed in 19 of 50 (38.0%) cases (9 weak positive and 10 strong positive). Besides the cytoplasm and cell membrane, nuclear staining was observed in 3 of 10 strong-positive cases. FGFR3 was further detected in non-neoplastic duct epithelial cells or duct papillomatosis in 5 strong-positive cases. No significant correlation was observed between FGFR3 expression and specific clinicopathological/molecular parameters. In contrast, FGFR3 expression was found to be significantly associated with overall survival in our cohort. Conclusions: FGFR3 expression in invasive breast cancer was not found to be significantly associated with specific clinicopathological/molecular parameters, but might be used as a candidate marker for a poor prognosis.

Wereport a 48-year-old man with thrombosis of the portal and superior mesenteric vein and inferior vena cava associated with primary antiphospholipid syndrome (APS). Primary APSwas diagnosed by a positive reaction with anticardiolipin antibody (aCL) and the absence of any evidence suggesting the presence of other disease states known to be associated with aCL. A coeliac angiography showed obstruction of the portal and superior mesenteric vein with prominent collaterals and cavernous transformation. Femoral vein angiography showed total obstruction of the external iliac vein and inferior vena cava, and dilation of the pelvic veins, with contrast mediumin the lumbar vein. This case is noteworthy as a report of primary APSaccompanied by extensive abdominal and pelvic venous thrombosis.(Internal

Rosuvastatin treatment was associated with significant reductions in plasma concentrations of TC, LDL-C, and TG, urine and plasma oxidative stress markers, and plasma hs-CRP in these hypercholesterolemic patients.