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The miRNAs, miR-15a and 16-1, were recently identified to be located in the critical region of del(13q14) [9]. The pathophysiologic role of these miRNAs is further underscored by the phenotype of genetically engineered mice carrying a targeted deletion of the mir-15a/16-1 locus in combination with a deletion of the noncoding RNA gene DLEU2. These animals develop a monoclonal B-cell lymphocytosis-like disorder, CLL, and lymphoma, suggesting that the miRNAs 15a and 16-1 indeed play a role in CLL leukemogenesis [11]. Deletions of the long arm of chromosome 11 (del(11q)) can be found in ?25% of chemotherapy-na?ve patients with advanced disease stages and 10% of patients with early stage disease [12, 13]. These deletions frequently encompass band 11q23 harboring the gene ATM, which encodes for the proximal DNA damage response kinase ATM. In addition, http://www.selleckchem.com/products/epz-5676.html patients carrying a del(11q) clone typically show a bulky lymphadenopathy, rapid progression, and reduced overall survival [14]. Interestingly, some of the poor prognostic features of del(11q) seem to be overcome by the use of chemoimmunotherapy [15]. Trisomy 12 is observed in 10�C20% of CLL patients. However, the genes involved in the pathogenesis of CLLs carrying a trisomy 12 are largely unknown. Furthermore, the prognostic relevance of trisomy http://www.selleck.cn/products/Staurosporine.html 12 remains a matter of debate [16]. Deletions of the short arm of chromosome 17 (del(17p)) are found in 5�C8% of chemotherapy-na?ve patients. These deletions almost always include band 17p13, where http://www.selleckchem.com/products/ly2109761.html the prominent tumor suppressor gene TP53 is located. CLL patients carrying a del(17p) clone show marked resistance against genotoxic chemotherapies that cannot be overcome by the addition of anti-CD20 antibodies in the context of state of the art chemo-immunotherapy [15]. Mutations of TP53 are found in 4�C37% of patients with CLL, and have been associated with very poor prognosis (ultra-high risk) in a number of studies [17]. Among cases with confirmed del(17p), the majority show mutations in the remaining TP53 allele (>80%). In cases without del(17p), TP53 mutations are much rarer, but have a similarly detrimental effect on chemotherapy response and overall survival [16]. TP53 mutations are also associated with higher genomic complexity in CLL, indicating that a crippled DDR promotes a ��mutator phenotype�� in CLL [16]. The recently reported whole genome sequencing projects in CLL have revealed a number of recurrent somatic gene mutations that occur in parallel to the above-mentioned structural genomic aberrations. These include the genes NOTCH1, MYD88, TP53, ATM, SF3B1, FBXW7, POT1, CHD2, and others [13, 18]. Of note, TP53, ATM, POT1, and CHD2 encode for proteins critically involved in DNA damage signaling and DNA repair [19].