Detection of cryptic chromosomal lesions including acquired segmental uniparental disomy in advanced and low-risk myelodysplastic syndromes

Copy neutral loss of heterozygosity: a novel chromosomal lesion in myeloid malignancies

“…46,48,66 This is particularly helpful in cases with normal cytogenetics, which is still associated with a wide range of clinical outcomes in individual patients, such as patients with intermediaterisk AML and a normal karyotype, some mixed MDS/MPN such as chronic myelomonocytic leukemia (CMML), 49 and JAK2-negative MPN. 58,72 The technical aspects of the SNP-A technology, including not requiring cell culture, provides a significant increase in the number of evaluable samples, particularly in hematologic malignancies associated with bone marrow fibrosis, through the use of peripheral blood cells in selected situations.…”

“…With the broader application of SNP-A came the realization as to how widely spread this balanced acquired lesion is in various malignancies, including AML, MDS, MPN, and the overlap syndromes but also ALL, CLL, and multiple myeloma 5,31,[46][47][48]55,[66][67][68] (Table 2). Representative examples of SNP-A karyograms of acquired areas of UPD found particularly frequently in myeloid malignancies from our studies are illustrated in Figure 4.…”

Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance

“…8 Another study showed that 82% of MDS patients harbor gains and losses detected by SNP arrays, whereas conventional cytogenetics detected alterations in 50%. 9 In addition, UPD was found in 33% of the patients. In both studies, first correlations of genomic imbalances including UPD with survival indicated that the presence of these may correlate with a shorter survival.…”

“…In both studies, first correlations of genomic imbalances including UPD with survival indicated that the presence of these may correlate with a shorter survival. 8,9 This high rate of UPDs in MDS was recently challenged in a study that showed, when using buccal DNA samples from the same patients as controls, that only a small number of the potential loss of heterozygosity regions represent tumor-specific UPDs and gains and losses. 10 In that report only 4/33 cytogenetically normal cases had additional alterations.…”

Defining prior therapy in myelodysplastic syndromes and criteria for relapsed and refractory disease: implications for clinical trial design and enrollment

“…14 Furthermore, when newer tools, such as array-based techniques for globally assessing single nucleotide polymorphisms and loss of heterozygosity, have been applied to MDS, these technologies have uncovered a broad range of previously cryptic chromosomal changes, identifying abnormalities in up to 80% of patients and providing "leads" for future experiments, underscoring the biologic complexity and diversity of these diseases. [15][16][17] It is anticipated that newly recognized genetic lesions will be incorporated into future iterations of MDS prognostic scoring systems, though their complexities may necessitate formal, online nomograms, as are used for prostate cancer progression probabilities (http://prostatecancerinfolink.net/tips-tools/kattannomograms), rather than back-of-the-envelope calculations.For several reasons, physicians, scientists, and regulatory officials are paying increasing attention to MDS. Aging of the population and the resultant increasing number of MDS diagnoses, 18,19 recognition that MDS is at least as common as acute myeloid leukemia (AML), and the encouraging precedent of 3 drugs achieving FDA approval for MDS-related indications since 2004 are resulting in a wave of clinical trials of novel treatment approaches and combinations of drugs.…”