Research articles

The authors present a workflow that allows the simultaneous measurement of the whole exome and the transcriptome by next-generation sequencing from formalin-fixed paraffin-embedded tissue sections that were analyzed by matrix-assisted laser desorption ionization mass spectrometry imaging. The data and analyses demonstrate the feasibility and reproducibility of this approach, which expands the possibilities of multi-omics integration in cancer research.

Siglec-15 is normally expressed by myeloid cells and upregulated in some human cancers and represents a promising new target for immunotherapy. The aim of this study was to develop an immunohistochemical assay for Siglec-15 to be used as a companion diagnostic for future clinical trials. Here, the authors created and validated an assay with a novel recombinant antibody to the cytoplasmic domain of Siglec-15. This study may support development of a companion diagnostic assay to enrich for patients expressing the Siglec-15 target for therapy.

Multiplexed ion beam imaging by time-of-flight (MIBI-TOF) uses secondary ion mass spectrometry to image dozens of proteins simultaneously in the same tissue section. The authors undertook a validation study, assessing concordance across serial sections of a tissue microarray that were independently imaged by MIBI-TOF or single-plex immunohistochemistry. They demonstrate that MIBI-TOF can generate consistent and quantitative annotations of clinically relevant cell states in archival human tissue and present a scalable framework for benchmarking multiplexed immunohistochemical approaches.

Soft tissue sarcomas are rare and aggressive neoplasms with limited models for laboratory-based studies. This study established eight models of soft tissue sarcomas, three malignant peripheral nerve sheath tumors, four undifferentiated pleomorphic sarcomas, and one unclassified spindle cell sarcoma. The new sarcoma cell lines are tools to elucidate molecular aberrations and improve treatment options for these difficult-to-treat sarcomas.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the formation of cysts within the kidneys. The authors generated PKD1 heterozygous knockout (PKD1^insG/+) pigs by CRISPR-Cas9 and somatic cell cloning techniques. The founder cloned animals and progeny showed the renal cyst formation from the neonatal stage, interstitial fibrosis of the renal tissue, and the presence of a premature asymptomatic stage. Their findings demonstrate that PKD1^insG/+ pigs recapitulate the characteristic symptoms of ADPKD.