Transcript CAP Cancer BioMarker Reporting CommitteeBiomarker

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)?