The researchers discovered just ten genetic mutations in the patient's tumour DNA that appeared to be relevant to her disease; eight of the mutations were rare and occurred in genes that had never been linked to AML. They also showed that virtually every cell in the tumour sample had nine of the mutations, and that the single genetic alteration that occurred less frequently was likely the last to be acquired. The scientists suspect that all the mutations were important to the patient's cancer.
Based on genetic testing with traditional methods at the study's outset, the patient was known to have two mutations that are common among AML patients, an indicator she had a typical subtype of the disease. The researchers sequenced the patient's full genome, meaning DNA from both sets of chromosomes, using genetic material obtained from a skin sample. This gave the scientists a reference DNA sequence to which they could compare genetic alterations in the patient's tumour cells, taken from a bone marrow sample.
The scientists then looked for genetic differences - points of single base changes in the DNA - in the patient's tumour genome compared with her normal genome. Of the nearly 2.7 million single nucleotide variants in the patient's tumour genome, almost 98 percent also were detected in DNA from the patient's skin sample, thus narrowing the number of variants that required further study to about 60,000.
The researchers identified the ten mutations by looking for single base DNA changes that altered the instructions for making proteins. Of the eight novel mutations discovered, three were found in genes that normally act to suppress tumour growth. Four other mutated genes appear to be involved in molecular pathways that promote cancer growth. Another gene alteration appears to affect the transport of drugs into the cell, and may have contributed to the patient's chemotherapy resistance.
The team also looked to see if the eight novel mutations in the patient's tumour genome also occurred in the DNA of tumour samples from 187 additional AML patients. None of those tumours had any of the eight mutations. This suggests that there is a tremendous amount of genetic diversity in cancer, the researchers argue.
MEDICA.de; Source: Washington University in St. Louis