Understanding the Genomics and Genetics of Cancer


Advances in genomic testing technologies are allowing scientists to better understand cancer and the mutations that drive it. This is possible through new types of testing that analyze each person’s cancer at a deeper level. Doctors use this information to diagnose and stage as well as find treatments that may be approved for those mutations.

Prior to the introduction of genomic testing, doctors diagnosed and determined treatment plans by using general information about the cancer, including its type, where it was located, the grade (how quickly the cancer cells are likely to grow and spread) and whether it had metastasized.

Today, genomic tests go a step further by finding mutations that may be driving the cancer. They do this by looking for biomarkers, changes in chromosomes, circulating tumor cells and gene mutations. The type of test (and the type of tissue used for testing) will vary, depending on the cancer involved and the information your doctor is seeking (see Table 1).

It may not be necessary or beneficial for all patients to have genomic testing, but it should be routine in all younger patients, especially if they have a no-smoking or light-smoking history. During the diagnostic process, your doctor will discuss the possibility of genomic testing with you if your cancer type has known mutations. Testing may be performed multiple times — at diagnosis, if the cancer progresses and sometimes during treatment to determine whether the cancer is responding.

Table 1 - Types of Genomic Testing

Test What the test does Sample type Symptoms and Signs
Comprehensive biomarker testing Looks or known biomarkers Tissue Determine treatment
Cytogenetic tests Looks for changes in chromosomes, including broken, missing, rearranged or extra chromosomes Tissue, blood or bone marrow Diagnose, plan treatment, determine treatment effectiveness
Fluorescence in situ hybridization (FISH) Looks at genes or chromosomes in cells and tissues and identifies where a specific gene is located on a chromosome, how many copies the gene are present and any chromosome abnormalities Tissue Diagnose, prognosis and evaluation of remission
Immunohistochemistry Tests for certain antigens (markers), such as proteins like PD-L1. It may also be used to determine the difference between cancer subtypes Tissue Diagnose
Immunophenotyping Tests for and identifies markers on cells Blood or bone marrow Diagnose and classify blood cell cancers
Karyotype Looks for abnormal numbers or structures of chromosomes Blood, bone marrow or tissue Diagnose and identify the Philadelphia chromosome found in chronic myelogenous leukemia
Liquid biopsy (also called circulating tumor DNA) Looks for cancer cells from a tumor that are circulating in the blood or for peices of DNA from tumor cells that are in the blood Blood Detect cancer at an early stage, plan treatment, determine treatment effectiveness
Microarray Generates a genetic profile fora given tissue sample that reflects the activity of thousands of genes Tissue Identify cancer subtypes
Multi-gene panel testing Studies many genes in a sample of tissue to find mutations in certain genes that may increase a person's risk of cancer Blood Find cancer, plan treatment or determine treatment effectiveness
Next-generation sequencing Tests multiple genes simultaneously Tissue Diagnose, prognosis and plan treatment
Polymerase chain reaction (PCR) Looks for certain changes in a gene or chromosome Blood, saliva, mucus or tissue Find and/or help daignose a cancer
Reverse transcription PCR (RT-PCR) Amplifies traces of DNA sequence so there are adequate quantities for analysis Blood, saliva, mucus or tissue To look for activation of certain genes, which may also help diagnose cancer

Understanding the Diagnostic Process

Obtaining and analyzing a biopsy sample are crucial to diagnosing the type of cancer you have because it will help your doctor determine the most effective type of treatment. In general, your doctor will follow these steps.

Step 1: A biopsy of tumor tissue will be taken. It can be done by several methods, and different tests require different amounts of tissue. Ask your doctor how your testing will be done before a biopsy to make sure enough tissue samples will be taken to meet the requirements of all the tests.

Step 2: The sample will be sent to a laboratory where a pathologist will look for the presence of cancer cells and document the size and location of the tumor, the number of lymph nodes with cancer cells and other important facts about the cancer. A pathologist is a doctor specially trained to diagnose disease by looking at cells under a microscope.

Step 3: If cancer cells are found, they will be extracted from the sample so the pathologist can determine the histologic type of the cancer. The six major histologic types are carcinomas, sarcomas, myelomas, leukemias, lymphomas and mixed types. In some instances, the pathologist may not be able to identify the histologic type because the tissue sample is too small. When this happens, another biopsy may be necessary.

Step 4: Specialized equipment will be used to sequence the tumor’s DNA and find any abnormalities. DNA sequencing determines the order of the four building blocks – called “bases” – that make up the DNA molecule.

Step 5: If abnormalities are found, they will be compared to known mutations.

Step 6: Results are returned to your doctor in a pathology report.

Step 7: If a known abnormality is found, your doctor may suggest treatment options that are approved to target the same mutations.

Step 8: Genomic testing may be repeated to monitor effectiveness or if your doctor suspects a recurrence or resistance.