Collect

FIXED (any specimen type):
  • tissue, paraffin embedded block
  • tissue, unstained slides (USS)
    • 5 USS cut 5-10µm thick at least 5mm X 5mm, preferably 10mm X 10mm tumor tissue
Recommendations: Send accompanying H&E 

Unacceptable Conditions

  • Paraffin blocks with low tumor percentage
  • Tissue fixed in heavy metal fixative
  • Decalcified tissue

Storage/Transport Temperature

Ambient temperature

Performed

Monday to Friday
Molecular Diagnostics

Remarks

TEST DESCRIPTION:  The Tumor Mutation Load (TML) Assay is a targeted next-generation sequencing assay that is designed for providing an accurate assessment of TMB (mutations/Mb). Studies have shown that tumors that have a high tumor mutation burden/load (TML or TMB) potentially have a better response to immunotherapy.   

TEST DETAILS:  A tumor mutation burden will be reported as a Mutation Load (Mutations/Mb).  The exact level of TML that should be used to predict response has not been definitively determined and may differ among tumor types. 
In clinical trials, 10 mut/Mb has been used (1,2), although other studies have also utilized 20 mut/Mb (3).  Pembrolizumab has been approved by the FDA for solid tumors with a TMB ≥ 10 mut/Mb in children and adults (5).

  • The assay detects low frequency somatic variants (SNPs and INDELs) from 409 genes, spanning ~1.7 Megabases (Mb) of genomic space, encompassing 1.2 Mb of exonic sequence.

LIMITATIONS:  The limit of detection for the TMB Assay is 20% tumor cellularity.

RECOMENDATIONS:  This assay can be ordered in conjunction with the Solid Tumor Precision Panel [STPP] -or- as a stand-alone test.

REFERENCES:
  1. Hellmann MD, et al. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med. 2018 May 31;378(22):2093-2104.
  2. Marabelle A, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020 Oct;21(10):1353-1365.
  3. Palmeri M,  et al. Real-world application of tumor mutational burden-high (TMB-high) and microsatellite instability (MSI) confirms their utility as immunotherapy biomarkers, ESMO Open, Volume 7, Issue 1,2022.
  4. Strickler JH, Hanks BA, Khasraw M. Tumor Mutational Burden as a Predictor of Immunotherapy Response: Is More Always Better? Clin Cancer Res. 2021 Mar 1;27(5):1236-1241.
  5. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors

Performed

Monday to Friday
Molecular Diagnostics

Methodology

The Oncomine Tumor Mutation Load (TMLassay uses DNA extracted from FFPE tumor tissue and treated with Uracil-DNA Glycosylase (UDG) to reduce potential FFPE-artifacts.  Indexed-pooled libraries are prepared using the Ion Chef instrument, clonally amplified and sequenced on the Ion S5™ Prime System.

Synonyms

  • Tumor Mutation Load
  • TML

CPT Codes

81479
**This test will either require prior authorization or a signed ABN

Test Build Information

OrderCode OrderName ResultCode ResultName CPT
TMBO Tumor Mutational Burden TMB Tumor Mutational Burden  81479
Collection

Collect

FIXED (any specimen type):
  • tissue, paraffin embedded block
  • tissue, unstained slides (USS)
    • 5 USS cut 5-10µm thick at least 5mm X 5mm, preferably 10mm X 10mm tumor tissue
Recommendations: Send accompanying H&E 

Unacceptable Conditions

  • Paraffin blocks with low tumor percentage
  • Tissue fixed in heavy metal fixative
  • Decalcified tissue

Storage/Transport Temperature

Ambient temperature

Performed

Monday to Friday
Molecular Diagnostics

Remarks

TEST DESCRIPTION:  The Tumor Mutation Load (TML) Assay is a targeted next-generation sequencing assay that is designed for providing an accurate assessment of TMB (mutations/Mb). Studies have shown that tumors that have a high tumor mutation burden/load (TML or TMB) potentially have a better response to immunotherapy.   

TEST DETAILS:  A tumor mutation burden will be reported as a Mutation Load (Mutations/Mb).  The exact level of TML that should be used to predict response has not been definitively determined and may differ among tumor types. 
In clinical trials, 10 mut/Mb has been used (1,2), although other studies have also utilized 20 mut/Mb (3).  Pembrolizumab has been approved by the FDA for solid tumors with a TMB ≥ 10 mut/Mb in children and adults (5).

  • The assay detects low frequency somatic variants (SNPs and INDELs) from 409 genes, spanning ~1.7 Megabases (Mb) of genomic space, encompassing 1.2 Mb of exonic sequence.

LIMITATIONS:  The limit of detection for the TMB Assay is 20% tumor cellularity.

RECOMENDATIONS:  This assay can be ordered in conjunction with the Solid Tumor Precision Panel [STPP] -or- as a stand-alone test.

REFERENCES:
  1. Hellmann MD, et al. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med. 2018 May 31;378(22):2093-2104.
  2. Marabelle A, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020 Oct;21(10):1353-1365.
  3. Palmeri M,  et al. Real-world application of tumor mutational burden-high (TMB-high) and microsatellite instability (MSI) confirms their utility as immunotherapy biomarkers, ESMO Open, Volume 7, Issue 1,2022.
  4. Strickler JH, Hanks BA, Khasraw M. Tumor Mutational Burden as a Predictor of Immunotherapy Response: Is More Always Better? Clin Cancer Res. 2021 Mar 1;27(5):1236-1241.
  5. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors
Ordering

Performed

Monday to Friday
Molecular Diagnostics

Methodology

The Oncomine Tumor Mutation Load (TMLassay uses DNA extracted from FFPE tumor tissue and treated with Uracil-DNA Glycosylase (UDG) to reduce potential FFPE-artifacts.  Indexed-pooled libraries are prepared using the Ion Chef instrument, clonally amplified and sequenced on the Ion S5™ Prime System.

Synonyms

  • Tumor Mutation Load
  • TML
Result Interpretation
Administrative

CPT Codes

81479
**This test will either require prior authorization or a signed ABN
RPS Interface Information

Test Build Information

OrderCode OrderName ResultCode ResultName CPT
TMBO Tumor Mutational Burden TMB Tumor Mutational Burden  81479