Cancer, the dreaded disease has continued to mystify both the scientific community and common man alike. Years of research have yielded valuable information about the molecular mechanisms and pathways involved in tumorigenesis, paving way for a cure. It is known that tumors are vastly heterogeneous and this has impeded the search for an effective therapy.
Siddhartha Mukherjee says in his book, The Emperor of All Maladies “Cancer was not disorganized chromosomal chaos. It was organized chromosomal chaos”. It seems that researchers from UK, Spain and Germany have managed to find some order in the disarrayed landscape of cancer.
The study is published in the The New England Journal of Medicine and focuses on a specific type of lesion namely, Myeloproliferative neoplasms. Myeloproliferative neoplasms (MPN) are a disorder in which the bone marrow produces too many blood cells. Since it is a disease of the blood, it is easier to obtain sufficient sample amounts for sequencing as compared to other solid tumours. Another advantage of studying myeloproliferative neoplasms is that they represent early stages of tumorigenesis, thus providing an ideal system to study if the order of different mutations can alter the prognosis and course of the cancer.
The researchers collected peripheral blood samples from 246 patients, grew individual colonies of different cell populations and sequenced single cells. They looked at mutations in two genes which are present in 10% of MPN patients, JAK2 which aids tumor progression and TET2 that works to suppress tumor growth. The study identified that in patients who acquire JAK2 mutation first as compared to TET2 first, had an increased risk of developing anomalous blood cell production and formation of blood clots. Their response to JAK2 inhibitor drugs are also different from the other group. This suggests that the order in which the mutations occur and not just a sum total of all mutations govern the clinical outcome and response to treatment in MPN patients. This research opens exciting avenues for the field of personalized medicine and offers similar opportunities to study solid tumors in a similar context.
Dr David Kent, one of the study’s lead authors, says: “This surprising finding could help us offer more accurate prognoses to MPN patients based on their mutation order and tailor potential therapies towards them.”The lead author of this study, Professor Tony Green adds: “This is the first time that mutation order has been shown to affect any cancer, and it is likely that this phenomenon occurs in many types of malignancy. These results show how study of the MPNs provides unparalleled access to the earliest stages of tumor development (inaccessible in other cancers, which usually cannot be detected until many mutations have accumulated). This should give us powerful insights into the origins of cancer.”
The original publication can be accessed here.