Cancer Biomarkers

5-HIAA (5-hydroxyindoleacetic acid)

A breakdown product of serotonin that is excreted through urine, which may be detected at elevated levels as a result of serotonin-producing carcinoid tumors. Urine can be tested for 5-HIAA to help with diagnosis and monitor disease. ^{1, 13, 14}

Also called: Serotonin metabolite

Associated cancers: Carcinoid tumors

ALK (anaplastic lymphoma kinase)

A receptor tyrosine kinase with an associated gene that, when mutated, can cause excessive growth and proliferation of cancer cells. Tumor tissue can be tested for ALK translocations which can help determine treatment and prognosis.^{1, 13}

Also called: ALK gene, ALK-Positive, ALK+

Associated cancers: Anaplastic large cell lymphoma, Non-small cell lung cancer (NSCLC)

AFP (alpha-fetoprotein)

A protein normally only detected in a fetus or pregnant women that, when detected in healthy adults, can suggest the presence of a tumor. Blood can be tested for AFP to aid diagnosis, prognosis, and treatment response. ^{1, 13}

Associated cancers: Germ cell tumors, Liver

Androgen Receptor (AR)

Receptors often found on prostate cancer cells that are typically dependent on binding with male hormones called androgens to grow and divide. Tumor tissue can be tested for these receptors to determine if treatment with androgen receptor blockers is appropriate.¹

Associated cancers: Prostate

B-cell Immunoglobulin

A genetically mutated (i.e., rearrangement) immunoglobulin that results in lack of diversity among B cells, or an increase in “clones,” potentially leading to uncontrolled cell growth and lymphoma. Blood, bone marrow, or tumor tissue can be tested for B-cell immunoglobulin rearrangement to aid diagnosis, evaluate treatment effectiveness, and check for recurrence.^{13, 14}

Also called: Immunoglobulin gene rearrangement, B-cell gene clonality, BCGR

Associated cancers: B-cell lymphoma

B2M (beta-2-microglobulin)

A protein found on the surface of most cells that is shed into the blood, particularly by B-cell lymphocytes and tumor cells. Blood, urine, and cerebrospinal fluid can be tested for B2M to determine prognosis and monitor treatment responses.^{13, 14}

Also called: β2-Microglobulin, Thymotaxin

Associated cancers: Chronic lymphocytic leukemia, Multiple myeloma, and some lymphomas

Beta-hCG (beta-human chorionic gonadotropin)

A hormone normally found in the blood and urine during pregnancy that, when detected in non-pregnant women, can indicate certain types of cancer. Blood or urine can be tested for beta-hCG to assess stage, prognosis, and response to treatment.^{1, 13}

Associated cancers: Choriocarcinoma, Liver, Lung, Ovarian, Stomach, Testicular

BTA (bladder tumor antigen)

A specific complement protein that may be detected as part of the body’s response to some urologic cancers. Urine can be tested for BTA to monitor disease progression.^{13, 14}

Also called: Human complement factor H related protein, CFHrp

Associated cancers: Bladder, Kidney, Ureter

BTK (bruton tyrosine kinase)

A non-receptor tyrosine kinase with an associated gene responsible for B cell development that, when mutated, can lead to ibrutinib resistance. Blood, bone marrow, or tissue can be tested for BTK alterations to inform treatment decisions. ¹⁵

Also called: BTK-acquired resistance

Associated cancers: B-cell lymphoma and leukemias

BCR-ABL Fusion Gene

An oncogene caused by a genetic translocation between chromosomes 9 and 22. Blood or bone marrow can be tested for the presence of the BCR-ABL fusion gene to confirm diagnosis, inform targeted therapy treatment decisions, and monitor disease status.^{1, 13}

Also called: Philadelphia Chromosome

Associated cancers: Acute lymphoblastic leukemia, Acute myelogenous leukemia, Chronic myeloid leukemia

BRAF

An intracellular kinase that plays a key role in the regulation of the mitogen-activated protein kinase (MAPK) cascade. When this gene is mutated, cells may grow uncontrollably. Tumor tissue can be tested for BRAF alterations to identify if a patient will benefit from treatment with certain targeted therapies.^{1, 13}

Also called: BRAF V600, BRAF gene

Associated cancers: Colorectal cancer, Cutaneous melanoma, Erdheim-Chester disease, NSCLC

BRCA1/BRCA2

A tumor suppressor involved in DNA damage repair that is mutated in various cancer types.  BRCA mutations can be germline and/or somatic. Blood and/or tumor tissue can be tested for BRCA alterations to determine if certain targeted therapies are appropriate.^{13, 16}

Also called: BRCA, Breast cancer susceptibility genes 1 and 2

Associated cancers: Breast, Ovarian, Prostate

C-kit/CD117

A protein found on the surface of many cells that is a type of receptor tyrosine kinase as well as a tumor biomarker. Tumor tissue, blood, or bone marrow can be tested for C-kit/CD117 alterations to aid diagnosis and treatment decisions.^{1, 13}

Also called: C-kit, CD117, stem cell factor receptor, KIT

Associated cancers: Acute myeloid leukemia, Gastrointestinal stromal tumor, Mast cell disease, Mucosal melanoma

Calcitonin

A hormone produced by C cells in the thyroid that, when detected at high levels, may indicate medullary thyroid cancer. Blood can be tested for calcitonin to aid in diagnosis, evaluate treatment response, and assess recurrence.^{13, 14}

Also called: Human calcitonin, Thyrocalcitonin

Associated cancers: Medullary thyroid cancer

CEA (carcinoembryonic antigen)

A protein that is present at very low levels in healthy adults, but which may be elevated with certain types of cancer. Blood can be tested for CEA to monitor how well treatment is working as well as assess cancer progression or recurrence.^{13, 14}

Associated cancers: Colorectal, some others

CD20

A protein found on B cells that may be detected at higher than normal levels in patients with certain types of B-cell lymphomas and leukemias. Blood can be tested for CD20 to inform treatment decisions.^{1, 13}

Also called: CD20 antigen

Associated cancers: Non-Hodgkin lymphoma

CA15-3/CA27.29

A protein produced by normal breast cells that may be measured at higher levels among patients with breast cancer. It is often associated with the related cancer antigen 27.29. Blood can be tested for CA15-3 to assess whether treatment is working or if the cancer has recurred but is not recommend as a reliable source for cancer detection.^{13, 14}

Also called: CA-Breast, Cancer Antigen-Breast

Associated cancers: Breast

CA19-9

A protein that exists on the surface of certain cancer cells. Blood can be tested for CA19-9 to assess whether treatment is working, particularly in pancreatic cancer cases, but is not recommended as a reliable independent source for cancer screening or diagnosis.^{13, 14}

Also called: Carbohydrate Antigen 19-9, Cancer Antigen-GI, CA-GI

Associated cancers: Bile duct, Gallbladder, Gastric cancers, Pancreatic

CA-125

A protein that is present on the surface of most ovarian cancer cells. Blood can be tested for CA-125 to inform diagnosis, assess treatment response, and evaluate recurrence.^{13, 14}

Also called: CA 125 tumor marker, Cancer antigen 125

Associated cancers: Ovarian

CD22

A protein found on B cells that may be detected at higher than normal levels in patients with certain types of B-cell lymphomas and leukemias. Blood or bone marrow can be tested for CD22 to aid diagnosis.^{13, 17}

Also called: CD22 antigen

Associated cancers: B-cell neoplasms, Hairy cell leukemia

CD25

A protein found on some white blood cells, including B cells and T cells, that may be detected at higher than normal levels in patients with certain types of lymphomas and leukemias. Blood can be tested for CD25 to inform treatment decisions.^{13, 18}

Also called: IL2RA, TAC antigen

Associated cancers: Hairy cell leukemia, Non-Hodgkin (T-cell) lymphoma

CD30

A protein found on some T cells and B cells involved in cell growth and survival which may be detected in higher than normal amounts on some types of cancer cells. Tumor tissue can be tested for CD30 to aid diagnosis and inform treatment decisions.^{1, 13}

Also called: CD30 antigen

Associated cancers: Mycosis fungoides, Peripheral T-cell lymphoma

CD33

A protein found on some myeloid cells that may be detected at higher than normal levels in patients with acute myeloid leukemia. Blood can be tested for CD33 to determine if specific targeted therapies are appropriate.¹³

Also called: CD33 antigen

Associated cancers: Acute myeloid leukemia

CgA (Chromogranin A)

A protein found inside neuroendocrine cells that may be detected at high levels in certain types of cancer, including carcinoid tumors. Blood can be tested for CgA to aid diagnosis, assess treatment responses, and evaluate recurrence.^{1, 13, 14}

Associated cancers: Neuroendocrine tumors, NSCLC, Prostate

Chromosome 17p Deletion

A genetic mutation resulting in the loss of the p53 tumor suppressor gene. Blood can be tested for this mutation to inform treatment decisions, as individuals with this mutation may not respond well to conventional therapies.^{13, 19}

Also called: TP53

Associated cancers: Chronic lymphocytic leukemia

EGFR (epidermal growth factor receptor)

A receptor tyrosine kinase with an associated gene that, when mutated, can cause excessive growth and proliferation of cancer cells. Tumor tissue or blood can be tested for EGFR to help determine prognosis and inform treatment decisions.^{1, 13, 14}

Also called: EGFR positive

Associated cancers: NSCLC

Estrogen Receptor (ER) / Progesterone Receptor (PR)

Receptors often found on breast cancer cells that are typically dependent on binding with the hormone estrogen and/or progesterone to grow and divide. Tumor tissue can be tested for these receptors to determine if treatment with hormone therapy and some targeted therapies is appropriate.^{13, 14}

Also called: ER and PR status, Hormone receptor status

Associated cancers: Breast

FGFR 1-4 (fibroblast growth factor receptor 1-4)

Receptor tyrosine kinases with an associated gene that, when amplified or mutated, can cause excessive growth and proliferation of cancer cells. Tumor tissue can be tested for FGFR alterations to inform treatment decisions.^{13, 20}

Also called: FGFR1, FGFR2, FGFR3, FGFR4

Associated cancers: Bladder, Breast, Endometrial, Lung, Ovarian

FLT3 (FMS-like tyrosine kinase 3)

A receptor tyrosine kinase with an associated gene that, when mutated, can cause excessive production of immature white blood cells. Blood can be tested for FLT3 alterations to determine if certain targeted therapies are appropriate.^{1, 13}

Also called: FLT3 gene

Associated cancers: Acute lymphoblastic leukemia, Acute myeloid leukemia

Gastrin

A hormone that increases gastric acid production and, when detected at elevated levels, may be an indicator of gastrinomas, also known as gastrin-producing tumors. Blood can be tested for gastrin to aid diagnosis, monitor treatment response, and detect recurrence.^{1, 13, 14}

Associated cancers: Gastrinoma

HER2/neu

A protein involved in normal cell growth that may be produced in excess amounts by cancer cells due to amplification of the HER2 gene or overexpression of the protein. Tumor tissue can be tested for HER2/neu overexpression to inform treatment decisions as HER2-positive tumors may be more aggressive and/or respond differently to treatment than HER2-negative tumors.^{1, 13, 14}

Also called: ERBB2, c-erbB-2, erb-b2 receptor tyrosine kinase 2, Human epidermal growth factor receptor 2

Associated cancers: Bladder, Breast, Ovarian, Pancreatic, Stomach

HRAS

A protein made by the HRAS gene, a member of the ras proto-oncogene family. These genes play an important role in EGFR signal pathways and, when mutated, can lead to abnormal cell growth. Tumor tissue can be tested for HRAS to inform treatment decisions.²¹

Also called: HRAS gene, H-Ras

Associated cancers: Bladder, Head and neck squamous cell carcinoma, Kidney, Thyroid

IDH1/IDH2

Enzymes involved in critical steps of the TCA cycle, a metabolic pathway. Mutations in these genes may cause cancer cells to grow and spread in the body. Bone marrow and blood can be tested for IDH1/IDH2 alterations to inform treatment decisions.^{1, 13}

Also called: Isocitrate dehydrogenase-1/2 gene

Associated cancers: Acute myeloid leukemia

Immunoglobulins (Ig)

Proteins found in plasma cells that, when mutated, divide uncontrollably, generating identical Ig clones and forming tumors. Blood and urine can be tested for elevated levels of a specific Ig, typically IgA or IgG, to help diagnosis, assess treatment response, and detect recurrence.¹

Also called: Monoclonal immunoglobulins, M proteins

Associated cancers: Multiple myeloma, Waldenström macroglobulinemia

JAK2

An intracellular kinase that regulates cytokine signaling. Mutations in this gene can lead to uncontrolled white blood cell production. There are over 50 known mutations which may result in this outcome, with the most common being V617F. Blood and bone marrow can be tested for JAK2 mutations to help with the diagnosis of certain leukemias.^{13, 14}

Also called: JAK2 gene, Janus Kinase 2, JAK2 V617F, JAK2 Exon 12 Mutation

Associated cancers: Leukemia

Ki67

A protein that can be detected when cells are growing and dividing and, thus, can be a marker for cell proliferation. Tumor tissue can be tested for Ki67 expression to aid with prognosis and treatment decisions.²²

Also called: Ki-67, Ki67 High

Associated cancers: Bladder, Breast, Prostate

KRAS

A protein made by the KRAS gene, a member of the ras proto-oncogene family. These genes play an important role in EGFR signal pathways and, when mutated, can lead to abnormal cell growth. Tumor tissue can be tested for KRAS alterations to inform treatment decisions.^{13, 14}

Also called: KRAS gene, K-Ras

Associated cancers: Colorectal, NSCLC

Lactate Dehydrogenase (LDH)

An enzyme involved in energy production found in most cells. Increased levels of LDH in blood may be an indicator of tissue damage somewhere in the body, including cancer. Blood can be tested for LDH to help assess stage, prognosis, and treatment response.^{13, 14}

Also called: Lactic acid dehydrogenase, LDH

Associated cancers: Germ cell tumors, Leukemia, Lymphoma, Melanoma, Neuroblastoma

MET

A protein and receptor tyrosine kinase made by the MET gene. When this gene is mutated, amplified or overexpressed, cells can grow uncontrollably. Mutations are often somatic but can be found as germline mutations in hereditary papillary renal carcinoma (HPRC). Tumor tissue can be tested for MET alterations to inform prognosis and treatment decisions.^{1, 23}

Also called: MET gene

Associated cancers: Head and Neck, Kidney, Liver, NSCLC

MGMT

A DNA repair enzyme that, when expressed at low levels, reduces DNA repair activity but also potentially increases sensitivity to alkylating chemotherapy. Tumor tissue can be tested for MGMT protein expression to aid with prognosis and treatment decisions.²⁴

Also called: MGMT promotor methylation

Associated cancers: Glioblastoma

Microsatellite instability (MSI) and/or Mismatch repair deficient(dMMR)

A form of genetic instability resulting in the loss of cellular repair functions. This may be due to hypermethylation of the MLH1 promoter, somatic mutations in mismatch repair genes, or germline mutations in mismatch repair genes (e.g., Lynch Syndrome). Tumor tissue can be tested for MSI/dMMR to guide treatment decisions and identify hereditary risk factors.^{1, 13, 25}

Also called: MSI-H/dMMR, MSI-High cancer, MSI-H

Associated cancers: Colorectal, Endometrial, Gastrointestinal, Ovarian, Skin

MLH1

A mismatch repair (MMR) gene that is responsible for making DNA repair proteins which, when deficient, may influence cancer growth. Blood can be tested for germline alterations of the MLH1 gene to diagnose hereditary cancer syndromes (e.g., Lynch Syndrome, Muir- Torre Syndrome). In addition, tumor tissue can be tested for somatic MLH1 hypermethylation to aid treatment decisions.²⁶

Associated cancers: Colorectal, Endometrial, Gastrointestinal, Ovarian, Skin

NRAS

A protein made by the NRAS gene, a member of the ras proto-oncogene family. These genes play an important role in EGFR signal pathways and, when mutated, can lead to abnormal cell growth. Tumor tissue can be tested for NRAS alterations to inform treatment decisions.²⁷

Also called: NRAS gene, N-Ras

Associated cancers: Acute myeloid leukemia, Lung, Melanoma

Neuron-specific enolase (NSE)

An enzyme found in the cytoplasm of neurons that is secreted when neurons are damaged. Blood can be tested for NSE to aid diagnosis and assess treatment response.²⁸

Associated cancers: Neuroblastoma, NSCLC

NTRK (Neurotrophic Receptor Tyrosine Kinase 1)

A receptor tyrosine kinase with an associated gene that, when mutated, can result in the production of abnormal proteins, TRK fusion proteins, which may spur cancer growth. Tumor tissue can be tested for NTRK fusions to inform treatment decisions.^{1, 29}

Also called: Neurotrophic tyrosine receptor kinase gene fusion, TRK fusions

Associated cancers: Brain, Breast, Colon, Head and neck, Lung, Soft tissue, Thyroid

p16

A protein made by the tumor suppressor gene, CDKN2. Deletions or mutations of this gene can lead to changes in p16 expression and, subsequently, potential cancer growth. Tumor tissue can be tested for p16 alterations to aid with prognosis and treatment decisions.³⁰

Associated cancers: Bladder, Cervical, Esophageal, Gliomas, Head and neck, Leukemia, Lung, Melanoma, Pancreatic

PCA3 mRNA

A protein and associated mRNA produced exclusively by the prostate which is significantly overexpressed in most prostate cancer cases. Urine (collected after digital rectal exam) can be tested for PCA3 mRNA to aid diagnosis by determining the need for a repeat biopsy after a negative biopsy.^{13, 14}

Also called: Prostate cancer antigen 3, Differential display code 3, DD3

Associated cancers: Prostate

PML/RARα Fusion Gene

An oncogene caused by a genetic translocation between chromosomes 15 and 17 that results in a new fusion gene and, subsequently, a new protein which leads to uncontrolled production of leukemic white blood cells. Blood and bone marrow can be tested for the  PML/RARα fusion gene or its transcript to help inform diagnosis and treatment decisions, as well as monitor residual disease and predict early relapse.^{13, 14}

Also called: Promyelocytic Leukemia/Retinoic Acid Receptor Alpha, PML-RARA, t(15;17)(q22;q12), AML-M3

Associated cancers: Acute promyelocytic leukemia

PAP (prostatic acid phosphatase)

An enzyme produced by the prostate that may be detected at increased levels in patients with prostate cancer. Blood can be tested for PAP to help diagnose poorly differentiated carcinomas.^{13, 14}

Associated cancers: Prostate

PD-L1

A protein found in high quantities on some cancer cells that binds to PD-1 receptors on T cells, preventing the T cell from killing the cancer cell. Tumor tissue can be tested for PD-L1 expression levels to determine if treatment with an immune checkpoint inhibitor is appropriate.^{1, 13}

Also called: PD-1/PD-L1

Associated cancers: Classical Hodgkin Lymphoma, Gastroesophageal junction, Liver, NSCLC, Stomach

PIK3CA

A gene which plays an important role in cell signaling that, when mutated, can lead to uncontrolled cell growth and cancer proliferation. Tumor tissue can be tested for PIK3CA mutations to inform prognosis and treatment decisions.³¹

Also called: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, p110-alpha

Associated cancers: Brain, Breast, Colorectal, Head and neck squamous cell carcinoma, Lung, Ovarian, Stomach

PSA (prostate-specific antigen)

An enzyme produced by the prostate that is normally released into the bloodstream in small amounts. When cancer is present, PSA may be detected at elevated levels. Blood can be tested for PSA to help with diagnosis, assess treatment response, and detect recurrence.^{13, 14}

Also called: Total PSA, Free PSA

Associated cancers: Prostate

PTEN Gene

A gene responsible for the production of a tumor suppressing protein that, when mutated, can lead to uncontrolled cell growth. Blood and/or tumor tissue can be tested for PTEN alterations to aid diagnosis, prognosis, and to inform treatment decisions.³²

Also called: PTEN, PTEN tyrosine phosphatase, MMAC1

Associated cancers: Breast, Endometrial, Glioblastoma, Lung, Melanoma, Prostate

RET

A receptor tyrosine kinase with an associated gene that, when mutated, can. result in uncontrolled cell growth. Tumor tissue can be tested for RET alterations to aid prognosis and inform treatment decisions.³³

Also called: RET gene, RET proto-oncogene, CDHF12/16

Associated cancers: Lung, Thyroid

ROS1

A protein and receptor tyrosine kinase made by the ROS1 gene. When this gene is mutated, or the ROS1 fusion protein is overexpressed, cancer cells may grow more quickly. Tumor tissue can be tested for ROS1 alterations to inform treatment decisions.^{1, 13}

Also called: ROS1 gene, ROS1 positive, ROS1+

Associated cancers: Bile duct, Colorectal, Glioblastoma multiforme, Ovarian, NSCLC, Stomach

Somatostatin Receptor

A receptor found on cells that binds to the hormone somatostatin and which may be found at high than normal amounts on certain cancer cells. Tumor tissue can be tested via diagnostic imaging for somatostatin receptors to inform treatment decisions.^{1, 13}

Associated cancers: Gastrointestinal or pancreatic neuroendocrine tumors

T790M

A receptor tyrosine kinase associated with the EGFR gene that, when mutated, may result in resistance to certain therapies. Tumor tissue or blood can be tested for T790M alterations to inform treatment decisions.³⁴

Also called: EGFR T790M

Associated cancers: Adenocarcinoma, Glioma, NSCLC

T-Cell Receptor Gene Rearrangement

A genetic mutation (i.e., rearrangement) that results in lack of diversity among T cells, or an increase in “clones,” potentially leading to uncontrolled cell growth and lymphoma. Blood, bone marrow, tumor tissue, body fluid, or blood can be tested for T-cell receptor gene rearrangement to aid diagnosis and possibly detect or evaluate residual disease.

Also called: T-cell gene clonality, TCGR, TCR gene rearrangement

Associated cancers: T-cell lymphoma

TPMT (Thiopurine S-methyltransferase)

An enzyme that metabolizes a class of drugs called thiopurines. Blood or a buccal swab can be performed to determine the current level of the enzyme in the blood and/or identify a potential germline mutation which leads to little or no TPMT activity in the body. These tests will help determine if treatment with thiopurines is appropriate given the potential toxicities that may result from low TPMT levels.^{13, 14}

Also called: TPMT RBC, TPMT genotype TPMT phenotype

Associated cancers: Acute lymphoblastic leukemia

Thyroglobulin

A protein produced by the thyroid that may be detected at elevated levels in the case of thyroid papillary and follicular cancers. Blood can be tested for thyroglobulin to evaluate treatment response and detect recurrence.^{13, 14}

Also called: Tg, TGB

Associated cancers: Thyroid

UGT (UDP-glucuronosyltransferase)

An enzyme that metabolizes a topoisomerase I inhibitor called irinotecan – a common cancer therapy. Blood or a buccal swab can be performed to determine the current level of the enzyme in the blood and/or identify a potential germline mutation which leads to little or no UGT activity in the body. These tests will help determine if treatment with irinotecan is appropriate given the potential toxicities that may result from low UGT levels.^{13, 35}

Also called: UGT1A1 gene, UGT1A1*28/*28, UGT1A1*28 variant homozygosity, UGT1A1 poor metabolizer

Associated cancers: Colorectal