18 December 2023

A new way to distinguish different subtypes of Hodgkin’s lymphoma using DNA from tumours circulating in blood has been reported by scientists at the American Society of Hematology (ASH) Annual Meeting.  

Because malignant Hodgkin’s cells are difficult to measure in tissue samples, Dr Ash Alizadeh of Stanford University, USA, and his team looked at a new ‘liquid biopsy’ technique.

The team developed a highly sensitive method of genomic profiling for classic Hodgkin’s lymphoma from blood samples. Using this, they discovered that the concentration of circulating tumour DNA (ctDNA) is  shaped by a gene called DNASE1L3.

Next, they profiled 366 patients and were able to distinguish two distinct classic Hodgkin’s lymphoma genomic subtypes. Each had its own clinical and prognostic profiles.

In addition, they found a new group of mutations that could be targeted with existing treatments that block specific antibodies.

In a paper published last week in the journal Nature to accompany the talk at the ASH annual meeting, the team wrote: “Collectively, these results support the utility of non-invasive strategies for genotyping and dynamic monitoring of classic Hodgkin lymphoma as well as capturing molecularly distinct subtypes with diagnostic, prognostic, and therapeutic potential.”

Dr Alizadeh commented: “This approach offers our first significant look at the genetics of classical Hodgkin lymphoma.

“Compared with other cancers, finding Hodgkin lymphoma cancer cells or cancer DNA to study is like searching for a needle in a haystack. A patient can have a football-sized tumour in their chest, but only about 1% of the cells in the mass are cancer cells, with the remainder representing an inflammatory response to the tumour.

“This has made it very difficult to find the smoking guns that drive the disease.”

He added: “Surprisingly, we detected more cancer DNA in the blood than in the cancer tissue itself. That seemed hard to believe until we had analysed enough samples to show that it was reproducible.”


Alig SK, Esfahani MS, Garofalo A, Li MY, Rossi C, Flerlage T, Flerlage JE, Adams R, Binkley MS, Shukla N, Jin MC, Olsen M, Telenius A, Mutter JA, Schroers-Martin JG, Sworder BJ, Rai S, King DA, Schultz A, Bögeholz J, Su S, Kathuria KR, Liu CL, Kang X, Strohband MJ, Langfitt D, Pobre-Piza KF, Surman S, Tian F, Spina V, Tousseyn T, Buedts L, Hoppe R, Natkunam Y, Fornecker LM, Castellino SM, Advani R, Rossi D, Lynch R, Ghesquières H, Casasnovas O, Kurtz DM, Marks LJ, Link MP, André M, Vandenberghe P, Steidl C, Diehn M, Alizadeh AA. (2023) “Distinct Hodgkin lymphoma subtypes defined by noninvasive genomic profiling.” Nature, doi: 10.1038/s41586-023-06903-x

Link: https://www.nature.com/articles/s41586-023-06903-x

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