Recent advances in Next-Generation Sequencing (NGS) and digital PCR (dPCR) technologies have enabled low allele frequency detection with greater precision, allowing for non-invasive detection of cancer-associated somatic variants from circulating tumor DNA (ctDNA) in blood or plasma (i.e. liquid biopsy). Due to high heterogeneity in cancer cells and the low prevalence of ctDNA in blood and plasma, there is an immediate need for a reproducible source of ctDNA-mimetic reference material for use in assay development, limit-of-detection (LOD) assessment, quality assurance, and proficiency testing. Current commercially available ctDNA reference standards are developed using two principal methods, each with its own limitations. Sonication of cancer cell line DNA does not mimic naturallyoccurring ctDNA fragment properties...

In the era of personalized medicine, with an increasing need for molecular testing, cytologic specimens comprise a crucial component in providing prognostic & predictive information for clinical management of lung cancer patients. Fine needle aspirate (FNA) of the lung is the most common sampling method which provides good quality nucleic acid for downstream molecular testing. However, due to the lack of reference standards mimicking FNA specimens, there is a lack of validation of different assays & standardization of the specimen across laboratories. Cytopathology reference material can be employed for assay development, quality assurance & proficiency panels to validate assay performance & understand cross-site and inter-operator variabilities across different laboratories..

1. In the era of personalized medicine, precision diagnostics and molecular profiling significantly influence clinical decisions in therapeutic treatment. 2. It has been established that 3-35% of cancer-related premature deaths can be prevented with better screening methods. 3. Cell line-based reference standards provide a renewable reproducible, and therefore reliable source of control or reference materials.

Cancer is a heterogeneous disease in which hundreds of genes, and many thousands of mutations, have been implicated in oncogenesis. As we enter an era of precision tumor profiling, there is a significant need for molecular reference standards that can be employed for assay development and quality assurance in order to validate assay performance, and understand cross-site and inter-operator reproducibility. Cell-line based reference standards are ideal for this application, since they represent a biologically-relevant, reproducible, and renewable source of control materials. With this in mind, we have engineered a reference bank of cell lines that contain over 100 oncogenic point mutations, insertions, and deletions...

1. In the era of personalized medicine, precision diagnostics and molecular profiling significantly influence clinical decisions in therapeutic treatment. 2. It has been established that 3-35% of cancer-related premature deaths can be prevented with better screening methods. 3. Cell line-based reference standards provide a renewable reproducible, and therefore reliable source of control or reference materials.

Fine-needle aspiration cytology has been increasingly used as the first tool in the evaluation of several diseases. Although cytology has a relevant role in the discrimination between benign and malignant lesions, conventional slides cannot lead to 100% conclusive results. It was hoped that the introduction of liquid-based cytology (LBC) would improve the efficacy of cytology through standardization, quality improvement, and the possibility of carrying out ancillary techniques on the residual stored material. In recent decades, the application of genomic alterations has been studied on cytologic samples with feasible and reliable results. The molecular analysis offers a powerful aid to define the best clinical or surgical approaches and follow-up for patients. In recent years, the application of different ancillary techniques has been carried out on conventional slides even though LBC represents a useful additional and alternative method for molecular testing.

With the expanding role of targeted therapy in patients with solid tumors, pathologists face the daunting task of having to maximize limited volume tissue obtained by fine needle aspiration for a variety of molecular tests. While most molecular studies on fine needle aspiration samples have been reported using cellular material, recent studies have shown that a substantial amount of DNA can be retrieved from the supernatant fluid of aspirate needle rinses after cell pelleting for cytospin or cell block preparations. In routine clinical workflow, the supernatant is discarded; however this fluid may provide a complementary source of DNA for tumor mutational profiling.

With the expanding role of targeted therapy in patients with solid tumors, pathologists face the daunting task of having to maximize limited volume tissue obtained by fine needle aspiration for a variety of molecular tests. While most molecular studies on fine needle aspiration samples have been reported using cellular material, recent studies have shown that a substantial amount of DNA can be retrieved from the supernatant fluid of aspirate needle rinses after cell pelleting for cytospin or cell block preparations. In routine clinical workflow, the supernatant is discarded; however this fluid may provide a complementary source of DNA for tumor mutational profiling.

Our understanding of cellular targets for cancer treatment and biomarkers for cancer detection has expanded exponentially over the last decade. Cytopathology sampling is frequently used in the diagnosis of non-small cell lung cancer (NSCLC),and there are several challenges in procuring and analyzing such specimens for molecular testing. This article explores these challenges.

Molecular testing is essential for the diagnostic workup of patients with advanced non–small cell lung cancers. Cytology specimens from minimally invasive procedures, such as endobronchial ultrasound–guided transbronchial needle aspiration, are often the only available samples for these patients. The implementation of molecular diagnostic testing, and in particular next-generation sequencing–based testing, on these cytologic specimens is currently an evolving field for lung cytopathology. The application of these molecular analyses on tyrosine kinase inhibitor–resistant non–small cell lung cancers raises unique technical, biologic, and clinical challenges.