Researchers led by Brigitte Gomperts at the University of California, Los Angeles, show that interleukin-13 induces epigenetic changes in allergic airway inflammation. Using transgenic mice, the researchers overexpressed IL13, finding that it led to DNA methylation changes in 177 genes. "We have found that IL13 expression in the airways is associated with coordinate changes in the methylation status of promoters of a large number of gene components of the IL13 transcriptome, consistent with an epigenetic regulatory function of gene methylation in allergic airway inflammation," the researchers write, adding that "interventions that manipulate the epigenome of the asthmatic lung may provide highly effective therapies in the future."

Also in the American Journal of Translational Research, Lei Nie from the University of Texas MD Anderson Cancer Center and his colleagues review the roles of long, non-coding RNAs, particularly during cancer development. LncRNAs can mediate epigenetic modifications and directly regulate target gene transcription. In cancer, there is increasing evidence that "lncRNAs are crucial players in a variety of tissue carcinogenesis, invasion, and metastasis," and can be categorized as either onocgenic or tumor-suppressors, Nie et al. write. "Characterization of oncogenic and tumor suppressor lncRNAs is an attractive field, which will lead to new markers of cancer diagnosis and identification of novel therapeutic targets," the authors add.

Albrecht Stenzinger from the University Hospital Heidelberg in Germany and his colleagues discuss their assessment of HER2 status diagnostic guidelines in the Journal of Molecular Diagnostics. Using a statistical simulation approach, the researchers looked into how the diagnosed HER2/chromosome 17 ratios are affected by sample size, signal distribution, and method used to calculate the ratio. "The analysis we present shows the limitations of the current recommendations for an imprecision not inflicted by the laboratory method but the data analysis and therefore underlines the importance of rigorous data analysis standards," Stenzinger et al. write.

Mutations in the mitochondrial gene ATPase6 occur frequently in Chinese patients with osteosarcoma, report researchers led by Qiao-Nan Guo from the Third Military Medical University in Chongqing, China, in an early online Experimental and Molecular Pathology article. Guo and colleagues sequenced the ATPase6 genes from 39 osteosarcoma samples, finding mutations in 24 of them that occurred at 27 different sites. Of the mutations seen, 19 were novel, though they occurred at low levels. In addition, the researchers noted that there was no association between the mutations and histopathological subtype. "MtDNA ATPase6 mutations may play a role in the tumorigenesis and development of osteosarcoma," the researchers write. "Further studies of the biochemical consequences of mtDNA ATPase6 mutations in osteosarcoma will provide insight into the roles of mitochondria in osteosarcoma tumorigenesis."

N-acetylglucosaminyltransferases V, or GnT-V, may be a marker for hepatocellular carcinoma as well as a possible treatment target for the disease, say Ting Wei from Southern Medical University in Guangzhou, China, and colleagues. To study the role of GnT-V in hepatocellular carcinoma, the researchers developed short hairpin RNAs targeting the GnT-V gene and transfected them into a HepG2 cell line. The researchers also examined clinical samples. From this, Wei et al. report that when GnT-V is down-regulated, the "proliferation, migration, invasion, and metastasisof HepG2 cells" is inhibited, and that GnT-V expression is more frequently seen in hepatocellular carcinoma than in liver cirrhosis or normal liver tissue. In addition, GnT-V expression increases as the cancer progresses. "These data from HepG2 cell line and clinical tissue all implied that GnT-V expression was positively related with malignancy in HCC," Wei et al. say. "Down-regulation of GnT-V may suppress the malignancy of HCC, so GnT-V may be both a differentiation marker and a potential target for the treatment of HCC."

In the Journal of Clinical Pathology, Antonino Carbone and Paolo De Paoli from Italy's National Cancer Institute review the role that viruses may play in carcinogenesis, and describe pathological and diagnostics techniques. Epstein-Barr virus, Kaposi's sarcoma-associated herpes virus, and human papillomavirus are all associated with carcinogenesis, and there are more sensitive ways to detect such infections including PCR analysis, gene chips, and other assays. "The future scenario we may have to face ahead of us in case the development of vaccines were feasible, and vaccination campaigns were effective, may consist of a 15 to 20 percent reduction of human malignant tumours worldwide," Carbone and De Paoli write.

Researchers led by Boston University School of Medicine's Meera Mahalingam report in Modern Pathology on their genetic and immunohistochemical assessment of desmoplastic melanoma subtypes. The researchers sequenced the RET, BRAF, and KIT genes of 43 samples desmoplastic melanoma — 24 of which were the pure subtype and 19 of which were mixed — and examined a number of immunohistochemical markers, including nestin, clusterin, SOX10, and CD117. "In this study, although we noted many similarities between these two subtypes on genetic analysis and immunohistochemistry, we also noted a distinct difference in CD117 expression, which has not been previously recognized," Mahalingam and her team write. "This observation requires further study and validation, but may, in part, begin to explain the significant phenotypic differences between these two groups."

Also in Modern Pathology, Luís Muñoz-Bellvis from Hospital Universitario de Salamanca and his colleagues say that primary colorectal cancer and its liver metastases have different genetic profiles. Using high-density SNP arrays, the researchers examined genetic changes present in primary colorectal cancer tumors and liver metastases. While primary and metastatic tumors from the same patient showed similar genetic changes, metastatic tumors had more chromosomal abnormalities. "We show the existence of relevant genetic differences between paired primary and metastatic colorectal tumors, which mainly consist of an increased frequency of genetic lesions of chromosomes that have been associated with metastatic colorectal cancer ... and, more interestingly, acquisition of new chromosomal abnormalities," Muñoz-Bellvis et al. say.

Chris Pemberton from the University of Otago in New Zealand and his colleagues report in Clinical Chemistry that the prepro-A-type natriuretic peptide signal peptide could be a biomarker of cardiovascular disease. Pemberton and his colleagues developed an immunoassay for the preproANP signal peptide and used it to determine the concentrations of the peptide in healthy heart tissue, circulating in healthy volunteers, in heart attack patients, and in patients undergoing catheterization. In addition, they analyzed the circulating ANPsp by tandem mass spec. In the heart attack patients, the researchers found that "plasma concentrations of ANPsp rose to peak values at 5 h after symptom onset, significantly earlier than myoglobin, creatine kinase-MB, and troponin."

University of Washington researchers led by Tomas Vaisar write in Clinical Chemistry that "LC-MRM/MS could be used to replace immunoassays in a variety of settings." They used a shotgun proteomic approach, LC-MRM/MS, and commercially available immunoassays to analyze apoliporoteins A-I, C-II, C-III, E, B, and J. While the shotgun approach did not correlate well with the immunoassay findings, the LC-MRM/MS approach did, the researchers found.