Sequencing 5 CTCs May Effectively Guide Cancer Treatment

Circulating tumor cell (CTC) analysis through long fragment reading (LFR) technology may be a cost-effective method for detecting targetable mutations in patients with cancer, according to a study published in Cancer Research.¹

Research into CTCs, which require a less invasive biopsy process than that for tissue samples, has yielded few clinic-changing results. For this study, researchers combined immunomagnetic enrichment/fluorescence-activated cell sorting and LFR to perform whole-genome sequencing on CTC samples from 1 patient with metastatic breast cancer.

The 61-year old patient had ER-positive/HER2-negative disease; she was treated with paclitaxel for 6 months followed by fulvestrant. At disease progression she received anastrozole. A blood draw was taken after she began anastrozole therapy and again 8 months later.

Genomic DNA from the 34 CTCs removed was parsed into 3072 compartments; each compartment was labeled with a unique barcode, combined, and sequenced.

Somatic mutations were detected in a little as 12% of CTCs. The authors noted that, given the comprehensiveness of LFR, the driver mutations and tissues of origin detected via this method may better guide treatment than most available gene panel–tests.

Given the prohibitive expense of performing LFR on 34 CTCs, the researchers replicated their findings using only 5 of the biopsied cells. Performing LFR on 5 cells only, the authors noted, is likely to cost about $3000.

The authors concluded that “using comprehensive and complete genetic evidence, provided by approaches such as described in this study, to guide treatment decisions that are effective, will ultimately lower medical costs and improve patient outcomes.”

Reference

1. Gulbahce N, Magbanua MJ, Chin R, et al. Quantitative whole genome sequencing of circulating tumor cells enables personalized combination therapy of metastatic cancer. Cancer Res. 2017;77(16):4530-41. doi: 10.1158/0008-5472.CAN-17-0688