When I first moved to metropolitan Washington, DC in 1992, I attended an oncology nursing conference at the National Cancer Institute. I remember hearing a pediatric immunologist talk about therapeutic approaches for rare childhood immune-compromising illnesses that universally led to premature death. His message was that of genetics and how advances in this field would change the future landscape of these uncommon pediatric death sentences.
He went on to predict that genetic engineering would also revolutionize cancer therapy such that in our future, there would be no need for surgery, radiation, or chemotherapy. The new science of genetics he said would eliminate cancer in our lifetime. I remember thinking that this prediction was ludicrous. But I now believe he just might be correct. The following offers further testimony to the genetic evolution in cancer care.
Non-Hodgkin lymphoma (NHL) is a heterogeneous group of lymphoid malignancies which can occur at any age, but is frequently diagnosed in two sub-groups: adolescent and young adults (AYAs, ages 15–39) and the elderly.1, 2 A recent study reporting the results of genomic profiling in AYAs and older adults with NHL revealed interesting findings.
While both groups had similar numbers of genomic alterations, the types of alterations were different in each group.3 ALK fusions were frequently seen in the AYA subset whereas the elderly demonstrated a genetic prevalence in histone modification. The authors postulated that NHL may have distinct genetic drivers within age subsets which in turn could influence the choice of targeted approaches based on the age of the patient.
Another review of the molecular genetics of NHL focused on the potential to isolate genetic abnormalities and associate them with risk and treatment outcomes, similar to what is done with the classification of leukemia.4 Case in point was the exemplar of Burkitt lymphoma (BL). The researchers cited knowledge of the almost universal overexpression of the oncogene MYC in BL. However, in addition to this MYC aberration, the three BL subtypes (i.e., endemic BL, predominantly seen in sub-Saharan Africa which is highly associated with Epstein-Barr virus, sporadic BL seen in Western countries and is usually Epstein-Barr virus-negative, and immune deficiency-associated BL, commonly seen in HIV-infected patients), exhibited distinctly different genetic aberrations in both number and type. This suggests that targeted therapies may need to be individualized by BL subtype and that not all BL will respond to therapies equivocally.
Acknowledging that the molecular basis of primary chemotherapy resistance is poorly understood, genomics has been investigated in acute myelogenous leukemia (AML) to determine its potential role in primary induction failure and chemotherapy resistance.5 Whole genome sequencing has begun to reveal the mutational landscape of relapsed AML in adults primarily pointing to preleukemic clonal persistence following induction chemotherapy. The overexpression of multiple altered genes has been correlated with primary chemotherapy resistance. This then requires the selection of targeted therapies having the potential to interfere with multiple pathways to control disease progression and prevent future relapse.
Cancer genetics has been described as the “new frontier” in cancer medicine. However, as advances mount in nature, scope and timeliness, the new frontier is quickly becoming our current reality. Stay tuned.
- Hochberg J, El-Mallawany N, Abla O. Adolescent and young adult non-Hodgkin lymphoma. Br J Haematol. 2016 May;173(4):637-50.
- Teras LR, DeSantis CE, Cerhan JR, et al. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA Cancer J Clin. 2016 Sep 12.
- Johnson A, Morosini D, Vergilio JA, et al. Unique genomic features in adolescent and young adult, as compared to older adult, non-Hodgkin lymphoma and potential therapeutic targets. Br J Haematol. 2016 Jun 12.
- Miles RR, Shah RK, Frazer JK. Molecular genetics of childhood, adolescent and young adult non-Hodgkin lymphoma. Br J Haematol. 2016 May;173(4):582-96.
- Brown FC, Cifani P, Drill E, et al. Genomics of primary chemoresistance and remission induction failure in paediatric and adult acute myeloid leukaemia. Br J Haematol. 2016 Oct 21.