Conventional Cancer Therapy and Whole Genome Sequencing

Current cancer therapies attempt to find, test and treat specific genetic mutations that are shared by groups of patients, but largely ignore individual differences. A new method of identifying cancer treatments, known as whole genome sequencing, is based on the idea that many cancers differ from patient to patient, and may have different genetic causes. The technique is expensive, experimental and not widely available, and has not cured any of the small number of patients who have tried it, but experts think it will become more common.Related Article »

Chromosomes

from normal cell

Mutation with no drug available

Mrs. McDaniel

TREAT

TARGET

COMPARE

SEQUENCE

SAMPLE

DEVELOP AND TREAT

COMPARE

Cancer-causing mutations with drug treatment available

Area of

detail

Areas of change

in cancer cell

Chromosome 2

Cancer drug

Radiation and

chemotherapy

Conventional Cancer Therapy

Drugs have been developed to treat a few dozen cancer-causing mutations. But if no targeted drugs are available for the patient’s mutation, radiation and chemotherapy may be used in an attempt to kill all fast-growing cells.

Researchers and drug companies tend to look for genetic mutations that occur frequently in people with specific types of cancer. The process can reveal similar mutations among patients, but can ignore unique and rare mutations.

Normal

CD28 gene

Normal

CTLA4 gene

Abnormal

duplication

and fusion

Finished genetic

sequences

A newly approved drug for melanoma, ipilimumab, was known to interfere with CTLA4. The drug seemed to suppress her cancer for two months, but then it returned. Her doctors searched for other targets, but Mrs. McDaniel died soon afterward.

But among the thousands of irrelevant differences, the team found a promising target. Two genes, CD28 and CTLA4, had fused in her cancer cells, and the fusion seemed to reverse the normal growth signals of her T cells.

TGen examined the data and found about 18,000 small genetic differences between the normal and cancer cells. Most of the differences were thought to have little or no significance for her cancer or possible treatment.

The laboratories determined the entire genetic sequence of her normal and cancer cells. The finished sequences, each a terabyte of information, were shipped on hard drives to TGen, a research institute, for analysis.

Beth McDaniel developed a rare form of cancer, a T cell lymphoma. After exhausting all the standard treatments, her family sent samples of her saliva and cancer tumors to Illumina and the Mayo Clinic.

Whole Genome Sequencing