Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
CAP Cancer BioMarker Reporting Committee Biomarker - Problem, ROI and Scope College of American Pathologists’ Biomarker Reporting Committee Problem 1. Clinicians think of biomarkers (e.g. : EGFR Exon 19 deletions) and need to understand non-standardized results 2. Bioinformaticists think of specific nucleotide changes 3. Cancer Registrars also need to understand non-standardized results, largely dependant on testing platform 4. From Report: How can clinicians connect nucleotide change with clinical guidelines, which are often expressed in terms of biomarkers? 5. From Lab: How can a molecular pathologist map from the nucleotide change to the biomarker? ROI • Eliminate bottleneck in reporting, by enabling algorithms to map from identified mutations to biomarkers. • Increase efficiency of Molecular Pathologists (a very limited resource). Scope • College of American Pathologists – Cancer BioMarker Reporting Templates – somatic, nucleotide biomarkers for clinical reporting Mapping from Machine Generated Sequence Variation to Cancer BioMarker Reporting Template Lung Cancer BioMarker Reporting Template Machine Readable to BioMarker Mapping + EGFR Mutational Analysis (Note B) + ___ No mutation detected (wild-type EGFR allele) + ___ Mutation identified (select all that apply) + ___ Exon 18 Gly719# + ___ Exon 19 deletion# + ___ Exon 20 insertion## + ___ Exon 20 Thr790Met### + ___ Exon 21 Leu858Arg# + ___ Other (specify)####: ______________________ + ___ Cannot be determined (explain): __________ Machine readable version from NGS: Chr: 7 Machine Seq: NC_000007.13 (platform NGS) genomic start: 55249071 Ref: C Molecular Allele: T Pathologist (platform ABI Seq) # This EGFR activation mutation is associated with response to EGFR tyrosine kinase inhibitors. ## This form of EGFR activating mutation is generally associated with resistance to EGFR tyrosine kinase inhibitors although insertions at or before position 768 can be associated with sensitivity. ### This mutation is typically secondary to other EGFR activating mutations and is associated with acquired resistance to tyrosine kinase inhibitor therapy. If seen in untreated/pretreated patients, may be present in the germline and indicate a hereditary cancer syndrome, in which case genetic counseling is suggested. #### There is limited data on response to EGFR tyrosine kinase inhibitors for many of the uncommon EGFR activating mutations. HGVS Clinical Genetics Representation: NM_005228.3: c.2369C>T NP_005219.2:p.Thr790Met Oncologist (platform kit) Human Understandable Biomarker: EGFR Exon 20 Thr790Met Multiple Transcript Reference Sequences Which is the canonical Transcript Reference Sequence & associated Exon placement??? Recommendations from HL7 Clinical Genomics & Anatomic Pathology Workgroups, NCBI, and LOINC/Lister Hill Center at NLM • For each Gene: provide a canonical reference sequence • For each Exon: derived from the canonical reference sequence • For each term ‘deletion’, ‘insertion’, ‘mutation’: define what is meant (e.g. mutation = DNA change type is ‘missense’, etc… OR if ‘Exon 20 deletion’ is it all deletions in Exon 20 or a specific list of Exon 20 deletions)?