Biomarkers / Algorithm

The multi-target stool DNA (mt-sDNA) is a colorectal cancer (CRC) screening modality that can detect 11 distinct biomarkers, and uses an algorithm to provide a qualitative result.1,2 A positive result may indicate the presence of colorectal cancer (CRC) or advanced adenoma (AA) and should be followed by a colonoscopy.2
mt-sDNA Biomarkers/Algorithm Download
Additional information on the Biomarkers and Algorithm utilized in the mt-sDNA test
mt-sDNA Algorithm and Biomarkers Download
A positive result may indicate the presence of colorectal cancer (CRC) or advanced adenoma (AA) and should be followed by a colonoscopy.2
Multiple biomarkers are entered into an algorithm to determine a composite score, and a negative result is a composite score less than 183; a positive result is a composite score greater than or equal to 1831a

mt-sDNA ALGORITHM INPUTS1

   Methylation Markers (Strand Counts)  KRAS Mutation Markers (Strand Counts) Hemoglobin 
BMP3 NDRG4
 β-actin
(ACTBb ANB) 		 KRAS1 KRAS2  β-actin
(ACTBb KRAS) 		Fecal Hb
ng/mL
STEP 1  Logistic Score Apply weighting factors
(for BMP3, NDRG4, ACTB ANB, KRAS1, and KRAS2 strand counts and fecal Hb ng/mL)
Logistic score regression formula → Logistic score  
 STEP 2  Sum of Scores DNA marker scores = Either “0” or “10” depending on
whether the DNA marker is below (“0”) or above (“10”) the 99.5 percentile of normal
Sum of scores = Logistic score + BMP3 score + NDRG4 score + KRAS1 score + KRAS2 score  
 STEP 3  Composite Score

Sum of scores subjected to an exponential equation → Range of values from 0 to 1000

 
 RESULT (-) Negative Result: Score <183  (+) Positive Result: Score ≥183
  • Multiple genetic markers (strand counts) and hemoglobin are scored1
  • A logistic score that applies weighting factors is added to other marker scores to determine the composite score1
  • The mt-sDNA test is qualitative, only providing a dichotomous "positive" or “negative” result1
  • A negative result is a composite score less than 183; a positive result is a composite score greater than or equal to 1831.  The composite score is not linear, a higher score does not implicate a stronger positive result.  
  • The algorithm provides needed context to determine the test result and associated risk1

11 Distinct Biomarkers Produce a Qualitative Result1

mt-sDNA Biomarkers algorithm infographic
  • Biomarkers do not have individually validated reference ranges, and each marker’s clinical significance is influenced by the other markers.1,2
  • Therefore, biomarker levels cannot be interpreted separately, and the algorithm must incorporate all biomarker measurements to produce a result.1,2
  • A positive result indicates that the biomarker combination has an increased association with CRC or advanced adenoma.1,2
  • Any positive result should be followed by a colonoscopy.1,2

A Single Stool Sample Can Provide Evidence Of CRC And Precancerous Growths1,3

Polyp progression and cancer biomarker implication depiction in a cross-section colon
  • As stool progresses through the colon and rectum, DNA sloughs from the lining of the colon and rectum as well as any blood that may be present1,3
  • This DNA and blood serve as the biomarkers evaluated by the test1,3
  • A single stool sample can present a snapshot of potential precancerous adenomas and colorectal carcinomas along the colon and rectum1,3
Learn more about the full Indications/Contraindications for the mt-sDNA test.   Please see complete prescribing information for Cologuard in the Cologuard Clinician Brochure.

Related Topics

Hb: hemoglobin, BMP3: Bone Morphogenetic Protein 3, NDRG4: N-Myc Downstream-Regulated Gene 4, KRAS: v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog.

References

1 Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med. 2014;370(14):1287-1297.

2 Cologuard Clinician Brochure. Exact Sciences Corporation. Madison, WI.

3 Ahlquist DA. Multi-target stool DNA test: a new high bar for noninvasive screening. Dig Dis Sci. 2015;60(3):623-633.

 

Footnotes

a The composite score is not linear, a higher score does not equal more risk above the 183 cutoff value.

bACTB is a reference gene for quantitative estimation of the total amount of human DNA in each sample.

Last updated: 11/19/2021