Genetic Mutations Key to Precision Medicine, Cancer Prevention

A recent study indicated that genetic mutations in blood cells caused by smoking and aging-related changed could be risk factors for a rare type of blood cancer that impacts immune cells. The findings could lead to new ways to diagnose and prevent the disease as well as advance precision medicine efforts.

Peripheral T cell lymphoma (PTCL) and angioimmunoblastic T cell lymphoma (AITL) are two uncommon types of cancer impacting immune T cells.

“AITL can be very aggressive, with only about one-third of patients surviving at least five years after their diagnosis,” first author Shuhua Cheng said in a press release. “To develop more effective therapies against AITL and PTCL, we need to learn more about what causes them.”

Cheng, a senior research associate at the Department of Pathology and Laboratory Medicine at Weill Cornell Medicine, and the team used next-generation genome sequencing to analyze 537 genes in 27 patients with AITL or PTCL. The researchers searched for genetic changes that could lead to T-cell tumors and secondary cancers.

Through the analysis, they found that about 70 percent of patients had mutations in precursor cells, most likely stem cells, in the bone marrow that could lead to a growing number of blood cells with these mutations and the early development of T-cell tumors. The mutation on the precursor cells is thought to be associated with aging.

Additionally, the team discovered mutations related to the tumor progression could be linked to smoking and second-hand smoke exposure. According to researchers, this suggests that avoiding smoking and second-hand smoke exposure could have a beneficial impact in preventing the development of these t-cell tumors.

The team also found that patients with a higher mutation burden of a specific gene associated with the early development of T-cell tumors were at a higher risk of developing additional types of tumors.

“Our results provide new information on how exposure to smoking may cooperate with early mutations in blood precursor cells to lead to the development of certain T-cell cancers,” said senior author Wayne Tam, Professor of Pathology and Laboratory Medicine at Weill Cornell Medicine.

“The findings suggest a potential new way to identify patients with AITL or PTCL who are most at risk of developing secondary tumors and may also help scientists and clinicians improve how these cancers are prevented, diagnosed and treated.”

By identifying the causes of AITL and PTCL, research can advance their precision medicine efforts while also developing methods to improve disease prevention.