Maybe we don't know JAK?

Schwarz, Luis J.; Balko, Justin M.

doi:10.1080/23723556.2016.1192713

Cited by 1 publication

(1 citation statement)

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“…In addition, although both assays had the ability to detect alterations in JAK2, this specific mutation was only detected in our patients by the ctDNA assay (N ¼ 2 patients), but not in any patient by tissue NGS. This finding could be an indication of activation of the JAK2/STAT3 pathway, which has been implicated as a marker for breast cancer cell motility, invasion, epithelialmesenchymal transition, and metastasis (20,21). However, because the JAK2 mutations were in V617F, the more likely explanation might be that this alteration reflected clonal hematopoiesis in these two elderly individuals (22).…”

Section: Discussionmentioning

confidence: 90%

Next-Generation Sequencing of Tissue and Circulating Tumor DNA: The UC San Diego Moores Center for Personalized Cancer Therapy Experience with Breast Malignancies

Shatsky

Parker

Bui

et al. 2019

Molecular Cancer Therapeutics

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Clinical-grade next-generation sequencing (NGS) of tissueand blood-derived circulating tumor DNA (ctDNA) allows assessment of multiple genomic alterations in patients with cancer. We analyzed ctDNA (54-70 genes) in 62 patients with advanced breast cancer (median ¼ five prior therapies); 38 also had tissue NGS (236-315 genes). Overall, 42 of 62 patients (68%) had detectable (characterized) ctDNA alterations (variants of unknown significance excluded), and 37 of 38 (97%) had tissue alterations. The median (range) number of characterized alterations in ctDNA was 1 (0-7), and in tissue, 4 (0-17). The most common alterations in ctDNA were in TP53 (37% of patients) and PIK3CA (23%), and for tissue, TP53 (37%) and PIK3CA (24%); EGFR amplification was seen in ctDNA (11%), but not in tissue. Concordance between ctDNA and tissue appeared higher if <6 months separated the sample acquisition, although small sample size precluded statistical validation. Overall, 32 of 67 tissue alterations (48%) were also detected in ctDNA; 35 of 72 ctDNA alterations (48%) were also in tissue. Excluding estrogen receptor and ERBB2, 41 of 62 patients (66%) had potentially actionable alterations in ctDNA, and 36 of 38 (95%), in tissue (with potential actionability based on either preclinical or clinical evidence). If !1 genomic alteration had ctDNA !5%, survival was shorter than if ctDNA was <5% (median, 6.7 vs. 17.9 months; P ¼ 0.01). In conclusion, tissue and ctDNA NGS reveal potentially actionable alterations in most patients. The genomic results of ctDNA and tissue NGS overlap, but there are differences, perhaps reflecting temporal spacing and tumor heterogeneity. ctDNA quantification also provides prognostic information.

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Section: Discussionmentioning

confidence: 90%