Novel Mutations in a Lethal Case of Lymphomatous Adult T Cell Lymphoma with Cryptic Myocardial Involvement

Abstract

The autopsy of a 65-year-old diabetic African American male revealed significant left myocardial involvement by adult T-cell leukemia/lymphoma (ATLL) despite normal pre-mortem fluorodeoxyglucose (FDG) uptake by positron emission tomography/computed tomography (PET/CT). Due to pre-existing diabetic cardiomyopathy with reduced ejection fraction (EF) and compatible imaging studies, cardiac lymphomatous involvement was not suspected. While peripheral blood was negative for leukemia, next-generation sequencing of a lymph node revealed at least eight novel mutations (AXIN1, R712Q, BARD1 R749K, CTNNB1 I315V, CUX1 P102T, DNMT3A S199R, FGFR2 S431L, LRP1B Y2560C and STAG2 I771M). These findings underscore a diagnostic pitfall in a rare lymphomatous variant of ATLL infiltrating myocardium and contribute to its molecular characterization.

The fellowship of the RING: BRCA1, its partner BARD1 and their liaison in DNA repair and cancer

“…Since these defects were demonstrated to be frequent in NB patients (van Engelen et al, 2009), Joucov and coworkers investigated this aspect and showed that depleting BARD1 (but also BRCA1) in frog embryos resulted in widely defective developmental phenotypes (including malformed neural tube and eye structures) (Joukov, Chen, Fox, Green, & Livingston, 2001), establishing a possible role of BARD1 in early organogenesis. In addition, very recently the BARD1 mutation R749K was reported in a fatal case of lymphomatous adult T-cell lymphoma with an ambiguous myocardial involvement (Hashemi Zonouz, Abdulbaki, Bandyopadhyay, & Nava, 2021).…”

Clinical Applications of Genomic Alterations in ATLL: Predictive Markers and Therapeutic Targets

“…A transcriptional analysis identified distinct transcriptomes between Japanese and North American cases [21], suggesting regional variations in ATLL pathophysiology. Several case reports identified novel mutations of ATLL [46,47]. Since clinical sequencing has been widely adapted, more novel mutations from other endemic areas will be identified through the analysis in future.…”