Patients with inherited thrombocytopenia or malignancy shoulder undergo ETV6 sequencing, with careful follow-up for identification of secondary cancers, according to findings published in the International Journal of Hematology.

Many cases of pediatric acute lymphoblastic leukemia (ALL) are characterized by ETV6/RUNX1 translocation, and as many as 0.8% of pediatric patients with ALL carry an ETV6 variant. A germline ETV6 variant was previously associated with heritable thrombocytopenia and predisposition to malignancy. For this case study, researchers evaluated clinical and sequencing data from a patient who presented with inherited thrombocytopenia and subsequent secondary malignancies.

The patient initially presented with inherited thrombocytopenia at age 11 months, and was diagnosed with ALL and mammary analog secretory carcinoma (MASC) at age 4 and 8 years, respectively; the MASC was diagnosed while the patient was in remission for ALL. Sequencing revealed an ETV6 c.641C > T (Pro214Leu) genetic aberration, the associated protein of which showed attenuated nuclear localization, increased protein degradation, and reduced transcription repression.

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The authors noted that while the patient’s father carried the same ETV6 mutation, he had not been diagnosed with cancer. The solid tumor noted in the present patient, an occurrence which has not been previously documented in this setting, may also have been a consequence of ALL treatment, according to the authors. Regardless, it may be important to sequence ETV6 among patients with inherited thrombocytopenia or malignancy and to schedule regular follow-ups to check for secondary cancers.

ETV6 pathogenic variants should be evaluated in families with inherited thrombocytopenia and predisposition to ALL,” the authors wrote. “It is important to provide genetic counseling and appropriate follow-up for these patients.”


Yoshino H, Nishiyama Y, Kamma H, et al. Functional characterization of a germline ETV6 variant associated with inherited thrombocytopenia, acute lymphoblastic leukemia, and salivary gland carcinoma in childhood [published online May 4, 2020]. Int J Hematol. doi: 10.1007/s12185-020-02885-y