BioOne Complete (complete.BioOne.org) is a full-text database of 200 subscribed and open-access titles in the biological, ecological, and environmental sciences published by nonprofit societies, associations, museums, institutions, and presses.

BackgroundNext generation sequencing tests (NGS) are usually performed on relatively small core biopsy or fine needle aspiration (FNA) samples. Data is limited on what amount of tumor by volume or minimum number of FNA passes are needed to yield sufficient material for running NGS. We sought to identify the amount of tumor for running the PCDx NGS platform.Methods2,723 consecutive tumor tissues of all cancer types were queried and reviewed for inclusion. Information on tumor volume, success of performing NGS, and results of NGS were compiled. Assessment of sequence analysis, mutation calling and sensitivity, quality control, drug associations, and data aggregation and analysis were performed.Results6.4% of samples were rejected from all testing due to insufficient tumor quantity. The number of genes with insufficient sensitivity make definitive mutation calls increased as the percentage of tumor decreased, reaching statistical significance below 5% tumor content. The number of drug associations also decreased with a lower percentage of tumor, but this difference only became significant between 1–3%. The number of drug associations did decrease with smaller tissue size as expected. Neither specimen size or percentage of tumor affected the ability to pass mRNA quality control. A tumor area of 10 mm2 provides a good margin of error for specimens to yield adequate drug association results.ConclusionsSpecimen suitability remains a major obstacle to clinical NGS testing. We determined that PCR-based library creation methods allow the use of smaller specimens, and those with a lower percentage of tumor cells to be run on the PCDx NGS platform.

No abstract

against advanced lung cancer, molecular targets are being explored. An emerging molecular target for lung cancer is the signaling molecule Akt as it is frequently activated in lung cancer. Akt is activated by a number of growth factor receptors and mediates processes such as proliferation, survival, migration, and metabolism. Three Akt isoforms (Akt1-3) exist in mammals and it remains unclear whether each isoform has distinct functions. To evaluate the function of Akt isoforms in lung cancer, a transgenic mouse model (SPC-IGFIR) where lung tumors were induced by elevated expression of IGF-IR and subsequent activation of Akt was used. SPC-IGFIR mice were mated with Akt1-/or Akt2-/mice to produce SPC-IGFIR mice lacking either Akt1 or Akt2. Lung tumorigenesis was suppressed in SPC-IGFIR/Akt1-/mice and enhanced in SPC-IGFIR/Akt2-/mice. Lung tumor cells in SPC-IGFIR/Akt2-/mice appeared to infilitrate the lungs to a greater extend than either SPC-IGFIR or SPC-IGFIR/ Akt1-/tumor cells which had a more nodular appearance. RNA sequencing revealed a number of genes and transcripts differentially expressed in the SPC-IGFIR/ Akt2-/lung tumors and several of these genes have been implicated in human NSCLC. Using 2 human NCSLC cell lines it was determined that an AKT1 selective inhibitor impaired cell survival more than an AKT2 inhibitor or a pan-AKT inhibitor. These results suggest that inhibition of Akt1 may represent a therapeutic strategy for lung cancer.