Cancer Biomarkers (Part 1)

what does ctDNA stand for?

circulating tumour DNA

NIH definition of a biomarker

biomarkers are any … than can be objectively … and evaluated as an indicator of a … … process, … process or … response to a … intervention

characteristics, measured, normal biological, pathogenic, pharmacologic, therapeutic

NCI definition of a biomarker

a biological … found in the …, … … or … that is a sign of a … or … process or of a condition or …

molecule, blood, body fluids or tissues, normal or abnormal, disease

4 main types of molecular biomarkers

1. DNA

2. RNA

3. proteins

4. metabolites

4 main types of characteristics acting as biomarkers

1. molecular

2. histologic

3. radiographic

4. physiologic

roles of biomarkers

1. … disease

2. … disease

3. predict …

4. determine …

5. monitor treatment …

6. monitor … and …

1. detect

2. stage

3. response to treatment

4. treatment efficacy

5. compliance

6. progression and recurrance

units of measurement for cancer biomarkers in the blood

ng/dL

cancer biomarkers based on criteria other than biomolecules

1. imaging biomarkers

2. pathological biomarkers

3. in silico biomarkers

what biomarker is commonly elevated in prostate cancer?

prostate specific antigen (PSA)

what is the most common EGFR mutation causing TKI resistance in NSCLC?

T790M

what does NSCLC stand for?

non small cell lung cancer

an ideal biomarker should be measured … and … using an assay with high analytical … and …

easily and reliably, sensitivity and specificity

does the left arrow show a false positive or negative?

false negative

does the right arrow show a false positive or negative?

false positive

first biochemical test for the detection of cancer

in 1847 … discovered a … protein in the urine of a … … patient where it was present in large … and was revealed by simple heat …

Bence Jones, globulin, multiple myeloma, quantities, denaturation

Bence-Jones protein (BJP) is a … produced free … … chain ( aka a …)

tumour, immunoglobulin light chain, paraprotein

in which body fluids is BJP found?

urine and serum

2 types of ulta-sensitive technologies

next generation sequencing and digital droplet PCR

next generation sequencing (NGS)

1. technology for determining the sequence of … and … to study … …

2. it enables the sequencing of … DNA strands at the same time

3. NGS achieves more … results with … amounts of sample

4. … … testing has enabled therapy decision based on genetic …

1. DNA and RNA, genetic variation

2. many

3. sensitive, smaller

4. gene panel, variants

digital droplet PCR (ddPCR)

1. method that provides absolute … of nucleic acids without needing a … curve

2. improves the … of qPCR and enables the detection of rare mutations such as … in a population of … type sequences

3. single PCR sample is partitioned into … droplets

4. each droplet undergoes PCR … and analysis separately

5. the droplets are the individually … and … as positive or negative for …

1. quantification, standard

2. sensitivity, SNVs, wild

3. 20,000

4. amplification

5. counted and scored, fluorescence

BRCA1 and BRCA2 gene mutations indicate risk for which 2 types of cancers?

breast and ovarian

… mutations in the … tumour suppressor gene causes … cancer

loss of function, APC, colorectal

mutations in the … and … mismatch repair genes lead to … … … cancer

MLH1 and MLH2, hereditary nonpolyposis colorectal

mutations in the … protooncogene accounts for 95% of … … … cancer cases

RET, hereditary medullary thyroid

cancer screening tests for the following types of cancer

1. cervical

2. breast

3. colorectal

4. prostate

5. ovarian

1. PAP and HPV

2. mammography

3. FOB and sigmoidoscopy

4. PSA

5. CA125

… … … (CEA) is a … involved in cell … normally produced during … development but not present in the … of healthy adults

carcinogenic embryonic antigen, glycoprotein, adhesion, fetal, blood

elevated levels of CEA are commonly used as biomarkers for monitoring … and … cancer

colon and pancreatic

CA125 is a … used for tracking … to treatment, … after treatment and detecting … of … cancer

glycoprotein, response, prognosis, recurrance, ovarian

elevated CEA levels are associated with other … not just pancreatic and colorectal, making it an unreliable biomarker for … or early …

carcinomas, diagnosis, detection

increased serum concentration of CA125 have also been observed in relatively … conditions such as … and other malignant cancers besides ovarian

benign, endometriosis

utilisation of CA125 does not demonstrate the clinical … and … required for ovarian cancer …

sensitivity and specificity, screening

increased … PSA levels are indicative of … cancer

serum, prostate

majority of PSA in the blood is bound to … … only a small portion of … PSA is not

comparison of … PSA to … PSA is used to assess the risk of cancer as the ratio is … in cancer meaning the levels of … PSA increase

serum proteins, free

free, total, decreased, free

elevated levels of PSA can also be attributed to prostate …, … and … … …

ths tests for PSA do not show the … and … required for prostate cancer …

infection, irritation and benign prostatic hypertrophy

sensitivity and specificity, screening

CA19-9 is a … used to monitor … cancer patients’ … to treatment and help detect …

elevated levels of CA19-9 have also been correlated with other cancers as well as … conditions such as … and … …

thus this biomarker does not exhibit sufficient … and … to be used for pancreatic cancer …

glycoprotein, pancreatic, response, recurrance

nonmalignant, pancreatitis and cystic fibrosis

sensitivity and specificity, screening

… and … are epitopes of the same protein antigen product of the … gene

CA15-3 and CA27-29, MUC1

which gene codes for CA125?

MUC16

CA15-3 and CA27-29 are biomarkers for … cancer and a high … level typically indicates … breast cancer and a large … …

breast, CA15-3, advanced, tumour burden

due to Ca15-3’s lack of … and … it has only been approved for monitoring patients’ … to treatment and to help detect …

sensitivity and specificity, response, recurrance