Table 1 A draft proposal for the minimal data needed for curation of evidence of a clinically actionable genomic event: evidence details

Gene

Gene implicated (Entrez gene id)

ESR1 (2099)

Event (gene-level or variant-level)

Genomic event such as SNV, indel, CNV, chimeric transcript, structural variation, epigenetic alteration, expression change, etc. See Table 2 for more details

chr6:g.152419922 T > A (Y537S)

Disease

Specific disease or disease subtype that is associated with this event and its clinical implication (Disease Ontology Identifier)

Estrogen-receptor positive breast cancer (DOID:0060075)

Evidence type

Category of clinical action implicated by event. See Table 3 for more details

Predictive

Evidence level

Levels of evidence for clinical actionability. See Table 3 for more details

Level B - clinical evidence

Evidence direction

A positive or negative value indicating whether the evidence statement supports or refutes a clinical association with the event

Positive - the evidence supports the association

Treatment (FDA status)

For predictive evidence, indicates the therapy for which sensitivity or resistance is indicated

Hormone therapy resistance

Actionability direction

Positive or negative association with treatment or diagnostic/prognostic end point

Negative - mutation is associated with resistance to therapy

Text summary (wiki-like)

Human readable interpretation. Free-form text summary of this event’s effect on cancer and potential clinical interpretations. This interpretation is the synthesis of all other information about an event and its relevance to clinical action and should be the living product of active discussion

Studies suggest ligand-binding-domain ESR1 mutants mediate clinical resistance to hormonal therapy and suggest that more potent estrogen receptor antagonists may be of substantial therapeutic benefit

Source

Literature where the event is described/explored (PubMed id)

PMID: 24185512