Risk assessment in newly diagnosed multiple myeloma patients (NDMM) is the first and the most crucial determinant of treatment. With the utilization of fiSH analysis as a part of routine practice, high riskMultiple Myeloma (MM) is defined as having at least one of the mutations related with poor prognosis including; t(4;14) t(14;16), t(14;20), del 17p, p53 mutation, gain 1q and del 1p. M-Smart MM risk stratification guideline by Mayo Clinic has proposed a concept similar to high grade lymphomas. Having two of the high risk genetic abnormalities were defined as double hit MM and having any three as triple hit MM. Based on these definitions which may bring a much more clinically relatable understanding in MM prognosis, we aimed to assess our database regarding these two concepts and their probable significance in terms of outcome and prognosis. We retrospectively evaluated 159 newly diagnosed multiple myeloma patients and their clinical course. Among these patients; twenty-four patients have one high risk determinant and also seven and two patients were classified as double hit MM and triple hit MM respectively. Overall survival (OS) of the patients with double hit MM was 6 months, 32.0 months for patients with single high risk abnormality and 57.0 months for patients with no high risk abnormality. Univariate analysis showed that Double Hit and Triple Hit MM is a predictive of low OS. Hazard Ratio of patients with one high risk abnormality was 1.42, double-hit MM patients was 5.55, and triple-hit MM patients was 7.3. Despite the development of novel drugs and their effects of prolonging survival, the treatment has not been individualized. Understanding the biology of each patient as a unique process will be the success of the treatment. As it is known that some MM patients harbor high risk genetic abnormalities according to fiSH analysis, we can continue the argument that some patients bring an even higher risk and that can be defined as double or triple hit MM.

No abstract

Molecular mechanisms governing the development of the human cochlea remain largely unknown. Through genome sequencing, we identified a homozygous FOXF2 variant c.325A>T (p.I109F) in a child with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is not found in public databases or in over 1000 ethnicity-matched control individuals. I109 is a highly conserved residue in the forkhead box (Fox) domain of FOXF2, a member of the Fox protein family of transcription factors that regulate the expression of genes involved in embryogenic development as well as adult life. Our in vitro studies show that the half-life of mutant FOXF2 is reduced compared to that of wild type. Foxf 2 is expressed in the cochlea of developing and adult mice. The mouse knockout of Foxf 2 shows shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Expressions of Eya1 and Pax3, genes essential for cochlear development, are reduced in the cochleae of Foxf 2 knockout mice. We conclude that FOXF2 plays a major role in cochlear development and its dysfunction leads to SNHL and developmental anomalies of the cochlea in humans and mice.

miRNAs are short noncoding RNA sequences that cause translational repression or mRNA degradation. A growing number of studies have sought new biomarkers in GBM that will be important in disease progression and prognosis and as potential therapeutic targets. miRNA-profiling studies in glioblastoma patients have found that aberrant miRNA expression can be used as a target to develop new biomarkers for disease detection and for determining prognosis or therapeutic response. In evaluating the tumor or its therapeutic response, genetic abnormalities such as mutations, epigenetic abnormalities, and aberrant miRNA expressions can be useful markers. This review summarizes the known miRNAs according their therapeutic importance and their use as disease progression biomarkers.