FAM53B truncation caused by t(10;19)(q26;q13) chromosome translocation in acute lymphoblastic leukemia

Abstract

RNA-sequencing of the patient's bone marrow detected fusion transcripts in which the coding sequence of the FAM53B gene (from 10q26) was fused to a genomic sequence (from 19q13) that mapped upstream of the SLC7A10 locus. Reverse transcription-polymerase chain reaction together with Sanger sequencing verified the presence of this fusion transcript. The FAM53B fusion transcript is not expected to produce any chimeric protein. However, it may code for a truncated FAM53B protein consisting of the first 302 amino acids of FAM53B together with amino acids from the 19q13 sequence. Functionally, the truncated FAM53B would be similar to the protein encoded by the FAM53B sequence with accession no. BC031654.1 (FAM53B protein accession no. AAH31654.1). Furthermore, the truncated protein contains the entire conserved domain of the FAM53 protein family. The chromosome aberration t(10;19)(q26;q13) detected in this study was previously reported in a single case of ALL, in which it was also the sole karyotypic change. Both patients entered complete hematological and cytogenetic remission following treatment.

Neoplasia-associated Chromosome Translocations Resulting in Gene Truncation

“…In 1985, De Braekeleer and coworkers reported an acute lymphoblastic leukemia carrying a t(10;19)(q26;q13) as the sole cytogenetic change (122). Thirty-two years later, we described the second case of acute lymphoblastic leukemia with t(10;19)(q26;q13) (89). Molecular analysis demonstrated that the coding sequence of the FAM53B gene (family with sequence similarity 53 member B) from 10q26 was fused to a genomic sequence from 19q13 that mapped upstream of the solute carrier family 7 member 10 (SLC7A10).…”

“…Many chromosome translocations resulting in truncated or fused genes leading to out-of-frame transcripts have been reported only once. These events might turn out to be recurrent if and when the second case, and then the third et cetera, is reported, as for the leukemias with t(8;19)/KAT6A::LEUTX described between 1988 and 1995 and t(11;20)/ZMYND8::RELA between 2013 and 2018 (33,37,38,40,53,67,(89)(90)(91)(92)(93)(94)(118)(119)(120)(121). In 1985, De Braekeleer and coworkers reported an acute lymphoblastic leukemia carrying a t(10;19)(q26;q13) as the sole cytogenetic change (122).…”

“…The reality of these gene fusions is then confirmed (or ruled out) using yet other methods such as FISH, PCR, and Sanger sequencing analyses (33,45,77,(84)(85)(86)(87)(88). This approach also has the advantage of not overlooking "non-canonical" fusion genes or rearranged genes that lead to truncated proteins (42,51,58,(89)(90)(91)(92)(93)(94).…”

“…Because no molecular analyses had been performed on the case from 1985 (122), we do not know whether the two reported translocations were identical at the molecular level. However, both patients had t(10;19)(q26;q13) as the only cytogenetic change, both were diagnosed with acute lymphoblastic leukemia, and both achieved complete hematologic and cytogenetic remission under antileukemic treatment (89,122).…”

Super-Enhancer Associated Five-Gene Risk Score Model Predicts Overall Survival in Multiple Myeloma Patients

“…FAM53B is a new vertebrate gene controlling cell proliferation ( Thermes et al, 2006 ). In acute lymphoblastic leukemia (ALL) cells, the FAM53B fusion transcript could code a truncated FAM53B protein, which was considered to be of great biological significance because of its entire conserved domain, even though the mechanism was unclear ( Panagopoulos et al, 2017 ). A four-gene model of MM consisting of FAM53B , KIF21B , WHSC1 , and TMPO could predict the overall survival of MM patients independently, and the expression of FAM53B was downregulated in high-risk patients compared to low-risk patients.…”