Expanding the CIViC Data Model to non-Gene based Variants

[arpaddanos]

Submitter Name

Arpad Danos

Submitter Affiliation

Washington University

Submitter Github Handle

arpaddanos

Additional Submitter Details

No response

Project Details

Required Knowledge

Some experience in cancer variant interpretation

[ahwagner]

10 interested

[arpaddanos]

For 2024 the discussion will be focused on the Factor type

[malachig]

Source of cancer related viruses:
https://gdc.cancer.gov/system/files/public/file/GRCh83.d1.vd1_virus_decoy.txt

[malachig]

One product of our discussion was a brainstormed list of possible factors to consider further:

• HRD (e.g. in ovarian, breast cancer)
• LOH (ovarian tumors)
• Tandem Duplication Phenotype
• HPV
• HTLV
• EBV (e.g. lymphoma)
• HIV
• HepB
• HepC
• KSHV
• Merkel Cell Virus
• CMV
• SV40
• H pylori (gastric)
• FNA C2 (gastric)
• T cell (High/"Hot" vs Low/"Cold")
• CD8 T cell
• M1/M2 ratio
• Memory like NK cell signature
• Mutation Signature (one variant for each Cosmic signature?)
• Methylation Signatures?

[Laveniya]

https://civicdb.org/evidence/11445/summary

An CNS tumor example where the methylation profile was used, albeit under gene name / molecular profile.

[cgrisdale]

Association of CD8+ T-cell and M1/M2 ratio scores with immunotherapy response (PMID: 33020056).

Mutation signature SBS3 and sensitivity to PARPi or platinum agents (PMID: 25719666, 26511885).

Glioma CpG island methylator phenotype (GCIMP) with prognostic implications (PMID: 29036500).

Global hypomethylation has prognostic and therapeutic implications in osteosarcoma (PMID: 35260776).

[arpaddanos]

FDA approval of pembrolizumab for TMB-high solid tumours: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors