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. 2020 Jan;41(1):7-16.
doi: 10.1002/humu.23926. Epub 2019 Oct 14.

Variation in nomenclature of somatic variants for selection of oncological therapies: Can we reach a consensus soon?

Cleo Keppens  1 , Véronique Tack  1 , Kelly Dufraing  1 , Etienne Rouleau  2 , Marjolijn J L Ligtenberg  3 , Ed Schuuring  4 , Elisabeth M C Dequeker  1
Affiliations

Variation in nomenclature of somatic variants for selection of oncological therapies: Can we reach a consensus soon?

Cleo Keppens et al. Hum Mutat. 2020 Jan.

Abstract

A standardized nomenclature for reporting oncology biomarker variants is key to avoid misinterpretation of results and unambiguous registration in clinical databases. External quality assessment (EQA) schemes have revealed a need for more consistent nomenclature use in clinical genetics. We evaluated the propensity of EQA for improvement of compliance with Human Genome Variation Society (HGVS) recommendations for reporting of predictive somatic variants in lung and colorectal cancer. Variant entries between 2012 and 2018 were collected from written reports and electronic results sheets. In total, 4,053 variants were assessed, of which 12.1% complied with HGVS recommendations. Compliance improved over time from 2.1% (2012) to 22.3% (2018), especially when laboratories participated in multiple EQA schemes. Compliance was better for next-generation sequencing (20.9%) compared with targeted techniques (9.8%). In the 1792 reports, HGVS recommendations for reference sequences were met for 31.9% of reports, for 36.0% of noncommercial, and 26.5% of commercial test methods. Compliance improved from 16.7% (2012) to 33.1% (2018), and after repeated EQA participation. EQA participation improves compliance with HGVS recommendations. The residual percentage of errors in the most recent schemes suggests that laboratories, companies, and EQA providers need to collaborate for additional improvement of harmonization in clinical test reporting.

Keywords: HGVS recommendations; biomarker variant reporting; colorectal cancer; external quality assessment; lung cancer; nomenclature; proficiency testing; round robin.

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Conflict of interest statement

C. K., V. T., and K. D. have nothing to declare. E. R. participated in advisory boards for Roche, Bristol‐Myers Squibb, and AstraZeneca. M. J. L. L. is consultant in advisory boards for AstraZeneca, Bayer, Janssen Pharmaceuticals, Merck, Nimagen, Roche, and received financial support from AstraZeneca and Bristol‐Myers Squibb (all fees to the institute). E. S. performed lectures for Illumina, Novartis, Pfizer, BioCartis; is consultant in advisory boards for AstraZeneca, Pfizer, Novartis, BioCartis; and received financial support from Roche, Biocartis, Bristol‐Myers Squibb, and Pfizer (all fees to the institute). E. M. C. D. received an unrestricted research grant from Pfizer Oncology to support the organization of the ESP Lung EQA schemes.

Figures

Figure 1
Figure 1
Percentage of HGVS compliant nomenclature (a) and reference sequences (b) related to used analysis techniques for the detection of EGFR, KRAS, and NRAS variants. Analyses only included entries for which corresponding method information was available. The number of scored entries differed for nomenclature versus reference sequence analysis given that for some participants no nomenclature was present on the written reports. HGVS compliant nomenclature was defined as all entries written according to HGVS format. HGVS compliant reference sequences included were those in LRG or NM format with inclusion of a version number. Noncommercial methods include fragment analysis, dideoxy or Sanger sequencing. An overview of commercial kits can be found in Table S3. Asterisks represent significant differences compared to other test methods by χ2 tests, *p < .05, **p < .01, ***p < .001. Abbreviations: EGFR, epidermal growth factor receptor; HGVS, Human Genome Variation Society; KRAS, KRAS proto‐oncogene GTPase; NGS, next‐generation sequencing; NRAS, NRAS proto‐oncogene GTPase
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