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. 2019 Jul 18;9(1):10426.
doi: 10.1038/s41598-019-47030-w.

Liquid biopsy-based comprehensive gene mutation profiling for gynecological cancer using CAncer Personalized Profiling by deep Sequencing

Affiliations

Liquid biopsy-based comprehensive gene mutation profiling for gynecological cancer using CAncer Personalized Profiling by deep Sequencing

Naoyuki Iwahashi et al. Sci Rep. .

Abstract

Liquid biopsies of circulating tumor DNA (ctDNA) have recently been used as a non-invasive diagnostic tool for detecting tumor-specific mutations. We present a study of ctDNA liquid biopsies in gynecological cancer using an ultrasensitive next-generation sequencing-based method for ctDNA detection named CAncer Personalized Profiling by deep Sequencing (CAPP-Seq). We performed CAPP-Seq with plasma-ctDNA obtained from 16 patients with gynecological cancer. In all cases, at least one non-synonymous somatic mutation was detected in the ctDNA. In the pre-treatment ctDNA, 4 of 16, 4/16, 5/16, 2/16, 2/16, and 2/16 patients had TP53, KRAS, APC, PIK3CA, BRCA1, and EGFR mutations, respectively. MET gene copy-number gains were detected in the ctDNA of 2 of 16 patients, and FISH analysis of the paired tumor samples confirmed these results. In 2 neoadjuvant chemotherapy-treated ovarian cancer patients, the changes in gene mutation patterns were associated with the treatment response. These findings suggest that CAPP-Seq-based liquid biopsies can be used for the genetic characterization of independent gynecological cancers with high frequency, and might be clinically useful for non-invasive tumor genotyping and therapeutic response monitoring.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
CAPP-Seq-based ctDNA analysis in patients with gynecological cancer. (A) The numbers of non-synonymous somatic mutations detected in the ctDNA of cancer patients according to disease stage. (B) The numbers of non-synonymous somatic mutations detected in the ctDNA of cancer patients according to cancer type. (C) Mutant allele fractions of ctDNA according to disease stage. (D) Mutant allele fractions of ctDNA according to cancer type. The median values for each group are represented by black bars. For patients in whom multiple alterations were detected, the highest value is shown.
Figure 2
Figure 2
Summary of ctDNA gene alterations identified by CAPP-Seq. *Gene mutations identified in both tumor and plasma samples.
Figure 3
Figure 3
FISH analysis of the MET gene. (A) Image of a FISH-positive specimen (COL1). (B) Image of a FISH-negative specimen (OVA4). (C) Number of MET signals/cell in FISH-positive specimens (COL1 and CER3). (D) Number of MET signals/cell in FISH-negative specimens (OVA4 and END1).
Figure 4
Figure 4
Changes in gene mutation profiles of ctDNA and clinical courses in NAC-treated ovarian cancer cases. Comparison of gene mutations in pre- and post-NAC ctDNA and the clinical courses of (A) an NAC-sensitive ovarian cancer case (OVA2) and (B) an NAC-resistance ovarian cancer case (OVA3).

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References

    1. Blair BG, Bardelli A, Park BH. Somatic alterations as the basis for resistance to targeted therapies. J Pathol. 2014;232:244–254. doi: 10.1002/path.4278. - DOI - PubMed
    1. Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011;11:426–437. doi: 10.1038/nrc3066. - DOI - PubMed
    1. McDermott U, Downing JR, Stratton MR. Genomics and the continuum of cancer care. N Engl J Med. 2011;364:340–350. doi: 10.1056/NEJMra0907178. - DOI - PubMed
    1. Misale S, et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature. 2012;486:532–536. doi: 10.1038/nature11156. - DOI - PMC - PubMed
    1. Murtaza M, et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 2013;497:108–112. doi: 10.1038/nature12065. - DOI - PubMed

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