Microscale Micro Krystal Klear # MSKK

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The identification of driver genetic alterations in key oncogenes and tumor suppressor genes plays an essential role in the diagnosis and treatment of many cancers. For more than a decade, biomarker analyses have been predominantly accomplished in solid tumors by sequencing tumor tissue collected at the time of surgical resection, diagnostic tumor biopsy, or cytology. However, in recent years, several studies have demonstrated that “liquid biopsies” could provide similar, and in some cases, more comprehensive information accompanied by a less invasive approach. Due to the significantly reduced procedure risk, they also enable longitudinal monitoring, which can substantially impact patient management. Here, we describe the analytical validation and clinical implementation of MSK-ACCESS, a hybridization capture-based NGS assay comprising 129 genes and capturing multiple classes of genomic alterations (SNV, indels, copy number alterations, and SV). Because of the scarcity of cfDNA material in the plasma and even smaller amounts of ctDNA, the development of this assay was guided by two key considerations: First, the assay had to enable the detection of low-frequency genomic alterations; and second, it had to incorporate the implementation of matched WBC sequencing to effectively filter out germline variants and CH mutations.

For comparisons of the prevalence of alterations across patients, we used mutation data from 47,116 solid tumor samples sequenced with MSK-IMPACT and considered only mutations that intersected with the MSK-ACCESS target exons. Comparisons were performed for select genes and cancer types where the alteration rate was greater than 3% by both MSK-ACCESS and MSK-IMPACT. Advances in molecular profiling have led to a rapid expansion in the number of predictive molecular biomarkers and associated targeted therapies, heightening the need for large-scale, prospective tumor profiling assays across all cancer types. The majority of comprehensive next-generation sequencing (NGS)-based profiling methods utilize tumor tissue as the primary specimen of choice for biomarker detection. Although widely used, obtaining an adequate tissue sample can be challenging in some cases due to the need for invasive biopsies that may pose an excessive risk to the patient. In addition, based on our clinical experience, 8.8% of the tissue submitted for molecular analysis is inadequate for testing due to low tumor cellularity, low DNA yield, or quality 1. Finally, a single tissue biopsy may not capture the full genetic heterogeneity of a patient’s cancer, and consequently, clinically actionable biomarkers may be overlooked even with the most sensitive and specific genomic assay. Taken together, a sole tissue-based genomic profiling approach may not be comprehensive and may limit treatment options for cancer patients. Jenkins, S. et al. Plasma ctDNA analysis for detection of the EGFR T790M mutation in patients with advanced non-small cell lung cancer. J. Thorac. Oncol. 12, 1061–1070 (2017).

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For MSK-ACCESS/MSK-IMPACT concordance analysis, only the clinically reported mutation calls from the first MSK-ACCESS sample per patient were used when multiple samples were sequenced. The union of clinically reported mutation calls from all samples sequenced on MSK-IMPACT for each patient was used given that MSK-ACCESS could potentially overcome tumor heterogeneity. This combined mutation list was re-genotyped as fragments, or overlapping reads, using GBCM, and the genotyped values were used for downstream analyses. Where mutations were reported in multiple IMPACT samples, the maximum genotyped VAF was used. Calls labeled as sub-threshold had at least two supporting fragments. Depending on the mask and your specific goals, you can also do a longer, deeper treatment, over the course of a few hours before your shower or even overnight. You can do this anywhere from once a month to once a week. Here are several recommended metrics and benefits resources you may find helpful in preparing your application.:

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After your first appointment, you need an enrollment ID and your medical record number (MRN) to create a MyMSK account. You can find your MRN on your printed visit guide for an upcoming appointment or on a billing statement from MSK. For anyone with MSK symptoms there is plenty that you can do yourself to help you to stay active, manage your symptoms, and carry on doing the things you want to do. Take a look at the advice put together by our expert MSK team to see what you can be doing to help yourself. This information should be used in conjunction with advice you have been given from your GP practice, healthcare practitioners and specialists.