Oncology Central

MLL gene mutations associated with improved survival in pancreatic cancer patients

A study published recently in Nature Communications reports on a new set of genes that predict improved survival following surgery for pancreatic cancer. The study, by the Translational Genomics Research Institute (TGen; USA) along with other major research institutes including Johns Hopkins University School of Medicine (MD, USA), Mayo Clinic (MN, USA) and Memorial Sloan Kettering Cancer Center (NY, USA), also demonstrated that detection of circulating tumor DNA (ctDNA) in the blood may provide an early indication of tumor recurrence.

The team performed whole-exome sequencing to observe the protein-coding regions of 24 tumors, as well as targeted genomic analysis of 77 further tumors. From these investigations, they demonstrated that mutations in chromatin-regulating genes MLL, MLL2, MLL3 and ARID1A were associated with improved survival in 20% of patients.

They also found ctDNA in the bloodstream of 43% of pancreatic cancer patients at the time of diagnosis by utilizing a liquid biopsy analysis. Importantly, the researchers also reported that ctDNA detection after surgery predicted clinical relapse and poor patient outcome. Moreover, use of the liquid biopsy detected cancer recurrence 6.5 months earlier than with CT imaging.

“These observations provide predictors of outcomes in patients with pancreatic cancer and have implications for detection of tumor recurrence, and perhaps someday for early detection of the cancer,” commented Daniel D Von Hoff (TGen), one of the study authors.

The study analyzed stage II tumors from patients who underwent potentially curative surgery. Since pancreatic cancer is hard to detect and therefore not usually diagnosed until late stages, only 15–20% of patients are candidates for tumor resection.

The study reported that noninvasive liquid biopsy analysis focusing on a few specific genetic alterations was able to diagnose a significant number of early-stage pancreatic cancers.

“We have identified MML genes as markers of improved prognosis for patients with pancreatic cancer,” Von Hoff remarked. “We have also shown that ctDNA in the blood of pancreatic cancer patients may provide a marker of earlier detection of recurrence of the disease.”

The report suggests that further studies should “evaluate more intensive therapies” for patients without MLL mutations or with detectable ctDNA following surgical tumor removal, along with interventional clinical trials.

Source: TGen press release




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