The translocations t(6;18;11)(q24;q21;q21) and t(11;14;18)(q21;q32;q21) lead to a fusion of the API2 and MALT1 genes and occur in MALT lymphomas

So far, only one variant translocation of the t(11;18)(q21;q21), the t(11;12;18) (q21;q13;q21), has been reported. We herein describe two new variant translocations, the t(6;18;11)(q24;q21;q21) and the t(11;14;18)(q21;q32;q21), occurring in mucosa-associated lymphoid tissue (MALT) lymphomas. In both cases, fluorescence in situ hybridization (FISH) and reverse transcriptase polymerase chain reaction (RT-PCR) revealed the presence of an 5′API2-3′MALT1 fusion product, encoded on the derivative chromosome 11. Exon 7 of API2 was fused with exon 5 of MALT1 in the t(11;14;18) and with exon 8 of MALT1 in the t(6;18;11). FISH revealed the involvement of the immunoglobulin locus in the t(11;14;18). Rapid amplification of cDNA ends (RACE)-PCR to detect the involved partner gene on 6q showed exclusively wild-type API2 and MALT1 sequences

Carbon ions Versus γ-Irradiation: The Telomeric Effect in Cancer Cells

International audienceThe higher biological effect of Carbon ions hadrontherapy (C+) is explained by the nature of the DNA damages. It is known that cell response to γ-irradiation (γ-IR), but not to C+, is correlated with telomere length in different type of cancer cells. Here, we propose that this " telomeric effect " must result from an effect of ROS in γ-IR compared to C+

#WouldYouBetOnIt - A cognitive approach to combat "fake news"

Many projects and campaigns against fake news try to tell people what is either right or wrong. This mainly leads to low acceptance rates by people. Therefore, we here claim that a proper way of working against fake news is to encourage people to think for themselves before spreading any type of news. People need to pause for a moment and ask themselves whether they believe this information to be true or not. This can be realized via nudging and boosting, concepts deeply rooted in Cognitive Psychology. We hope that this discussion paper will be adopted as an amendment for other projects and campaigns against fake news known from the literature in order to increase their value and impact

Major molecular response achievement in CML Patients can be predicted by BCR-ABL1/ABL1 or BCR-ABL1/GUS ratio at an earlier time point of follow-up than currently recommended.

Recent studies demonstrate that early molecular response to tyrosine-kinase inhibitors is strongly predictive of outcome in chronic myeloid leukemia patients and that early response landmarks may identify patients at higher risk for transformation who would benefit from an early switch to second-line therapy. In this study, we evaluated the ability of the control gene GUS to identify relevant thresholds for known therapeutic decision levels (BCR-ABL1/ABL1IS  = 10% and 0.1%). We then defined the most relevant cut-offs for early molecular response markers (transcript level at 3 months, halving time and log reduction between diagnosis and 3 months of treatment) using GUS or ABL1. We demonstrated that, although both control genes could be used (in an equivalent way) to accurately assess early molecular response, the BCR-ABL1/GUS level at diagnosis is impacted by the higher GUS copy number over-expressed in CML cells, thus negatively impacting its ability to completely replace ABL1 at diagnosis. Furthermore, we pointed out, for the first time, that it would be helpful to monitor BCR-ABL1 levels at an earlier time point than that currently performed, in order to assess response to first-line tyrosine-kinase inhibitors and consider a potential switch of therapy as early as possible. We evaluated this optimal time point as being 19 days after the start of treatment in our cohort

The t(14;18)(q32;q21)/IGH-MALT1 translocation in MALT lymphomas contains templated nucleotide insertions and a major breakpoint region similar to follicular and mantle cell lymphoma

The t(14;18)(q32;q21) involving the immunoglobulin heavy chain locus (IGH) and the MALT1 gene is a recurrent abnormality in mucosa-associated lymphoid tissue (MALT) lymphomas. However, the nucleotide sequence of only one t(14;18)-positive MALT lymphoma has been reported so far. We here report the molecular characterization of the IGH-MALT1 fusion products in 5 new cases of t(14;18)-positive MALT lymphomas. Similar to the IGH-associated translocations in follicular and mantle cell lymphomas, the IGH-MALT1 junctions in MALT lymphoma showed all features of a recombination signal sequence-guided V(D)J-mediated translocation at the IGH locus. Furthermore, analogous to follicular and mantle cell lymphoma, templated nucleotides (T-nucleotides) were identified at the t(14;18)/IGH-MALT1 breakpoint junctions. On chromosome 18, we identified a novel major breakpoint region in MALT1 upstream of its coding region. Moreover, the presence of duplications of MALT1 nucleotides in one case suggests an underlying staggered DNA-break process not consistent with V(D)J-mediated recombination. The molecular characteristics of the t(14;18)/IGH-MALT1 resemble those found in the t(14;18)/IGH-BCL2 in follicular lymphoma and t(11;14)/CCND1-IGH in mantle cell lymphoma, suggesting that these translocations could be generated by common pathomechanisms involving illegitimate V(D)J-mediated recombination on IGH as well as new synthesis of T-nucleotides and nonhomologous end joining (NHEJ) or alternative NHEJ repair pathways on the IGH-translocation partner

Identification of a perinuclear positioning element in human subtelomeres that requires A-type lamins and CTCF

The localization of genes within the nuclear space is of paramount importance for proper genome functions. However, very little is known on the cis-acting elements determining subnuclear positioning of chromosome segments. We show here that the D4Z4 human subtelomeric repeat localizes a telomere at the nuclear periphery. This perinuclear activity lies within an 80 bp sequence included within a region known to interact with CTCF and A-type Lamins. We further show that a reduced level of either CTCF or A-type Lamins suppresses the perinuclear activities of D4Z4 and that an array of multimerized D4Z4 sequence, which has lost its ability to bind CTCF and A-type Lamins, is not localized at the periphery. Overall, these findings reveal the existence of an 80 bp D4Z4 sequence that is sufficient to position an adjacent telomere to the nuclear periphery in a CTCF and A-type lamins-dependent manner. Strikingly, this sequence includes a 30 bp GA-rich motif, which binds CTCF and is present at several locations in the human genome