Yonsei Med J.  2019 Oct;60(10):914-923. 10.3349/ymj.2019.60.10.914.

Integrating a Next Generation Sequencing Panel into Clinical Practice in Ovarian Cancer

• Lee YJ
• Kim D
• Kim HS
• Na K
• Lee JY
• Nam EJ
• Kim SW
• Kim S
• Kim YT

• KMID: 2459144
• DOI: http://doi.org/10.3349/ymj.2019.60.10.914

Abstract

PURPOSE
Few efforts have been made to integrate a next generation sequencing (NGS) panel into standard clinical treatment of ovarian cancer. The aim of this study was to investigate the clinical utility of NGS and to identify clinically impactful information beyond targetable alterations.
MATERIALS AND METHODS
We conducted a retrospective review of 84 patients with ovarian cancer who underwent NGS between March 1, 2017, and July 31, 2018, at the Yonsei Cancer Hospital. We extracted DNA from formalin-fixed, paraffin-embedded tissue samples of ovarian cancer. The TruSight Tumor 170 gene panel was used to prepare libraries, and the MiSeq instrument was used for NGS.
RESULTS
Of the 84 patients, 55 (65.1%) had high-grade serous carcinomas. Seventy-three (86.7%) patients underwent NGS at the time of diagnosis, and 11 (13.3%) underwent NGS upon relapse. The most common genetic alterations were in TP53 (64%), PIK3CA (15%), and BRCA1/2 (13%), arising as single nucleotide variants and indels. MYC amplification (27%) was the most common copy number variation and fusion. Fifty-seven (67.9%) patients had more than one actionable alteration other than TP53. Seven (8.3%) cases received matched-target therapy based on the following sequencing results: BRCA1 or 2 mutation, poly ADP ribose polymerase inhibitor (n=5); PIK3CA mutation, AKT inhibitor (n=1); and MLH1 mutation, PD-1 inhibitor (n=1). Fifty-three (63.0%) patients had a possibility of treatment change, and 8 (9.5%) patients received genetic counseling.
CONCLUSION
Implementation of NGS may help in identifying patients who might benefit from targeted treatment therapies and genetic counseling.

Keyword

Next generation sequencing; ovarian cancer; targetable alterations

MeSH Terms

Cancer Care Facilities
Diagnosis
DNA
Genetic Counseling
Humans
Ovarian Neoplasms*
Poly(ADP-ribose) Polymerases
Recurrence
Retrospective Studies
DNA
Poly(ADP-ribose) Polymerases

Figure

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  Fig. 1 Pie chart of the distribution of actionable somatic alterations. HRR, homologous recombination repair.

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  Fig. 2 Mutation, copy number variation profiling. (A) Single nucleotide variants and indels. Color legend of the variations represented, including frameshift indel, inframe indel missense, and nonsense. Vertical lines indicate gene names; horizontal lines indicate cases with germline mutations. (B) Copy number variations and fusions. Color legend of the variations represented, including amplification, fusion. Vertical lines indicate gene names; horizontal lines indicate cases with germline mutations. (C) Homologous recombination repair (HRR)-related genes and The Cancer Genome Atlas druggable genes. Color legend of the variations represented, including single nucleotide variants, indel, and copy number variations. Vertical lines indicate gene names; horizontal lines indicate cases with germline mutations. (D) Number of mutations with six functional and targetable pathways. Vertical lines indicate the number of cases with mutations; horizontal lines indicate specific genes grouped according to pathways.

• 

  Fig. 3 CONSORT diagram. *ClinicalTrials. Gov Identifier: NCT03509246; †ClinicalTrials.Gov Identifier: NCT03414047. NGS, next generation sequencing; IHC, immunohistochemistry; PD-L1, programmed cell death-ligand 1.

• 

  Fig. 4 Clinical impact of next generation sequencing panel.

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