HL

Circulating free DNA can be used for genotyping – oral abstract in Classical Hodgkin Lymphoma at SOHO 2017

The fifth Annual Meeting of the Society of Hematologic Oncology (SOHO) took place at the Westin Galleria in Houston, Texas, between 13th–16th September 2017.

In 2012, SOHO was established and the society “aims to promote worldwide research, education, prevention, clinical studies and optimal patient care in all aspects of hematologic malignancies and related disorders.” SOHO has over 2,000 members and is led by a Board of Directors with six voting members, a Steering Committee of clinician-scientists, a Scientific Committee, and an Education Committee.

The 2017 meeting was a dynamic and informative event with internationally recognized speakers representing the spectrum of hem-onc diseases. This year, it is thought that over 1,000 physicians, nurses, and related healthcare specialists attended the 3.5-day event.

The seventh session of the meeting was dedicated to Hodgkin Lymphoma (HL), took place on 15th September 2017, and was co-chaired by Robert W. Chen, MD, from City of Hope, Duarte, California, USA, and Alison J. Moskowitz, MD, from Memorial Sloan Kettering Cancer Center, New York, New York, USA.

One oral abstract (HL-144) was presented during this session and was be given by Valeria Spina, PhD, from the Institute of Oncology Research, Bellinzona, Switzerland. Spina reported on a study that investigated if the mutational profile of Classical HL (cHL) can be determined using plasma Circulating Free DNA (cfDNA).

Key Highlights:
  • Included newly diagnosed pts (n=49), chemorefractory pts (n=32), and longitudinally samples pts during treatment (n=22)
  • All cases provided with cfDNA and paired germline DNA (gDNA); paired gDNA from macrodissected tumor tissue available for 12 pts
  • Proportion of mutations in cfNDA also found in gDNA = 86.4%
  • In newly diagnosed pts, the most frequently affected genes = STAT6 (41%), TNFAIP3 (35%), and ITPKB (32%)
  • ITPKB was specifically mutated in cHL across aggressive cases
  • Affected genes in newly diagnosed pts indicated molecular deregulation of specific pathways including: NF-kB (51%), PI3K/AKT (49%), and cytokine signaling (41%)
  • Refractory pts shared a very similar mutational profile as newly diagnosed pts
  • TET2 mutations (16%) were enriched in refractory pts and acquired at refractory progression
  • Longitudinal genotyping indicates that cHL follows a branching clonal evolution

Overall, this study found that cHL can be genotyped using cfDNA and follows a preferential branching evolution process. Furthermore, ITPKB was identified as a new gene specifically involved in cHL and acquisition of TET2 abnormalities appears to contribute to chemorefractory phenotype.

A study was recently published by Mao Li from West China Hospital, Sichuan University, Sichuan, China, and colleagues, which aimed to determine if the concentration and integrity if plasma cfDNA could aid in diagnosis and monitoring of progression in patients with HL and subtypes of Non-Hodgkin Lymphoma (NHL); read more here.

Abstract:

The mutational profile of classical Hodgkin Lymphoma (cHL) is poorly characterized, and the genetics and evolution of refractory disease is completely unknown.

References
  1. Spina V. et al. Genotyping of Classical Hodgkin Lymphoma on the Liquid Biopsy. Clinical Lymphoma, Myeloma, and Leukemia. 2017 Sep; 17(suppl 2):S323. DOI: http://dx.doi.org/10.1016/j.clml.2017.07.130.