Oncomine genomic panel — sample 22OM011 (DNA/RNA)
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LLC “Nano Medical Tehnologies”
68 Antonovycha St, Kyiv, Ukraine
Phone: +38 (044) 200-82-51
lifecode.come.ua
Patient: Zherlitsyna Anastasia Stanislavivna ORDER: 22B104
Date of birth: 25.04.1976 Received: 15.12.2022
Sex: Female Executed: 06.01.2023
Service: OncoMine - NGS study identifying thousands of gene hotspots and variants (SNVs, CNVs,
InDels, TMBs, MSIs, HRDs, gene fusions) associated with response to targeted and
immunotherapy
Block number: 48278/22
Number of tumor cells: 500-700
Percentage of tumor cells: ~80%
Results of molecular profiling
Identified gene variants (mutations, translocations, amplifications)
Allele Therapeutic significance
frequency If "yes"
Biological
Gene The detected variant (%) /
significance Yes/No OncoKB A group Sensitive./
Number of
of copies score Resist.
substances
MTAT- Translocation MTAT- 70358
CDKN2B_AS1 CDKN2B_AS1_004.M5 lines per Active No - - -
_004 A5 1 million
263 lines
Translocation KIF5B- MET
KIF5B-MET per 1 Active Yes 4 Sensitive
MET.K24M15 Inhibitors
million
284 lines
BRD3- Translocation BRD3-
per 1 Active No - - -
NUTM1 NUTM1.B10N2
million
Mutation
c.1668_1676delGTGGA
KIT
KIT AGGT 42,49% Active Yes 3B Sensitive
Inhibitors
(p.Gln556_Val559delin
sHis)
Mutation c.719A>G
TPMT 39,83% Active No - - -
(p.Tyr240Cys)
Mutation c.460G>A
TPMT 49,93% Active No - - -
(p.Ala154Thr)
Mutation c.1080G>C
PPM1D
(p.Gln360His)
License of the Ministry of Health of Ukraine No. 142 dated January 28, 2021
Genomic indicators (TMB, MSI, LOH)
Genomic marker Result Therapeutic significance
Low sensitivity to inhibitors
Mutational load (TMB) Low (4,82 Mut/Mb)
PD-1/PD-L1
Microsatellite indtability The microsatellite tumor is stable Low sensitivity to inhibitors PD-
(MSI) (MSS) 1/PD-L1
Loss of heterozygosity -
Unspecified
(LOH)
Summary of molecular profiling results
A mutation in the 11th exon of the KIT gene was detected in the tumor. KIT inhibitors such as
imatinib, sunitinib, regorafenib, and ponatinib have been approved for patients with gastrointestinal
stromal tumors (GIST) with such mutations. The clinical efficacy of these drugs in patients with
leiomyosarcoma is currently unknown, but from a biological point of view, they may be potentially
effective in this case.
Translocation of the MET gene was also detected in the patient. This translocation leads to the
activation of the met protein, so such a tumor can potentially be sensitive to the use of MET inhibitors.
However, given the low number of RNA with this translocation (263 lines per 1 million), it can be
assumed that this variant is subclonal, which makes it less likely to obtain a clinical effect from
targeted therapy. Furthermore, MET gene translocations are currently not a registered indication for
targeted therapy in any type of cancer.
In addition, mutations in the TPMT, PPM1D genes and MTAT-CDKN2B_AS1_004 and BRD3-
NUTM1 translocations were found in the tumor, which currently have no clinical and therapeutic
significance.
When assessing genomic parameters, the tumor was found to be microsatellite-stable (MSS) and to
have a low mutational load (TMB-Low), which is associated with a low potential efficacy of
immunotherapy with PD-1/PD-L1 inhibitors. The level of loss of heterozygosity (LOH) could not be
determined due to insufficient DNA quality in the sample, but given the absence of mutation in the
BRCA1/2 genes and other genes of the homologous recombination (HRR) system, the tumor is
potentially insensitive to PARP inhibitors.
*Method: Next Generation Sequencing (NGS)
*Set: Oncomine Comprehensive Assay Plus (Thermo Scientific)
*Sensitivity: 5% of mutant alleles
*Equipment: The Ion Proton Sequencer (Thermo Scientific)
Researched gene biomarkers Researched genomic biomarkers
165 genes with mutations (SNVs, In/Dels) in HRD – Determination of LOH (loss of heterozygosity) — at the gene
"hot spots" level and sample level
333 genes for amplification and deletion >1 mb of coding sequences to determine TMB (tumor mutational
(CNV) load)
227 genes with complete coding DNA
MSI-H/MSS microsatellite markers to determine MSI status
sequence (CDS)
49 genes for translocation (Fusions)
MET detection of exon skipping at the level of
DNA and RNA
License of the Ministry of Health of Ukraine No. 142 dated January 28, 2021
*Quality control: The coverage quality of target sequences is satisfactory
*Classification of biological significance: Oncomine database (Thermo Scientific)
*Classification of therapeutic significance: OncoKB (Memorial Sloan Kettering Cancer Center)
* Research results are not a diagnosis and require a doctor's consultation.
Performers:
Geneticist Shapochka D.O
License of the Ministry of Health of Ukraine No. 142 dated January 28, 2021