Candidate susceptibility variants in angioimmunoblastic T-cell lymphoma


Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma with a poor prognosis: the 5-year survival rate is approximately 30%. Somatic driver mutations have been found in TET2, IDH2, DNMT3A, RHOA, FYN, PLCG1, and CD28, whereas germline susceptibility to AITL has to our knowledge not been studied. The homogenous Finnish population is well suited for studies on genetic predisposition. Here, we performed an exome-wide rare variant analysis in 23 AITL patients. No germline mutations were found in the driver genes, implying that they are not frequently involved in genetic AITL predisposition. Potentially pathogenic variants present in at least two patients and showing significant (p < 0.01) enrichment in our sample set were found in ten genes: POLK, PRKCB, ZNF676, PRRC2B, PCDHGB6, GNL3L, TTC36, OTOG, OSGEPL1, and RASSF9. The most significantly enriched variants, causing p.Lys469Ter in a splice variant of POLK and p.Pro588His in PRKCB, are intriguing candidates as Polk deficient mice display a spontaneous mutator phenotype, whereas PRKCB was recently shown to be somatically mutated in 33% of another peripheral T-cell lymphoma, adult T-cell lymphoma. If validated, our findings would provide new insight into the pathogenesis of AITL, as well as tools for early detection in susceptible individuals.

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This work was supported by the Academy of Finland, Finnish Center of Excellence Program 2012–2017 [Grant Number 250345]. We wish to thank Heikki Metsola, Sini Nieminen, Alison Ollikainen, Marjo Rajalaakso, Sirpa Soisalo, Inga-Lill Svedberg, and Iina Vuoristo for their indispensable assistance.

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Correspondence to Lauri A. Aaltonen.

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Donner, I., Katainen, R., Kaasinen, E. et al. Candidate susceptibility variants in angioimmunoblastic T-cell lymphoma. Familial Cancer 18, 113–119 (2019).

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  • Angioimmunoblastic T-cell Lymphoma (AITL)
  • AITL Patients
  • Spontaneous Mutator Phenotype
  • Peripheral T-cell Lymphoma (PTCL)
  • AITL Cases