The cytogenetic alterations in renal oncocytoma (RO) are poorly understood. We analyzed 130 consecutive RO for karyotypic alterations. Clonal chromosome abnormalities were identified in 63 (49%) cases, which could be categorized into three classes of mutually exclusive cytogenetic categories. Class 1 (N = 20) RO had diploid karyotypes with characteristic 11q13 rearrangement in balanced translocations with 10 or more different chromosome partners in all cases. We identified recurrent translocation partners at 5q35, 6p21, 9p24, 11p13-14, and 11q23, and confirmed that CCND1 gene rearrangement at 11q13 utilizing fluorescence in situ hybridization (FISH). Class 2 RO (N = 25) exhibited hypodiploid karyotypes with loss of chromosome 1 and/or losses of Y in males and X in females in all cases. The class 3 tumors comprising of 18 cases showed diverse types of abnormalities with the involvement of two or more chromosomes exclusive of abnormalities seen in classes 1 and 2 tumors. Furthermore, karyotypically uninformative cases were subjected to FISH analysis to identify classes 1 and 2 abnormalities. In this group, we found similar frequencies of CCND1 rearrangement, loss of chromosome 1 or Y as with karyotypically abnormal cases. We validated our results against 91 tumors from the Mitelman database. Correlation of clinical data with all the three classes of ROs showed no clear evidence of overall patient survival. Our findings support the hypothesis that RO exhibit three principal cytogenetic categories, which may have different roles in initiation and/or progression. These cytogenetic markers provide a key tool in the diagnostic evaluation of RO.

Abstract Christopher B. Anderson1, Michael Lipsky1, Subhadra V. Nandula2,3, Christopher E. Freeman2, Thomas Matthews2, Catlin Walsh2, Gen Li1, Matthias Szabolcs2, Mahesh M. Mansukhani 2, James M. McKiernan1, Vundavalli V. Murty 2 1Departments of Urology, 2Pathology and Cell Biology, Columbia University Medical Center, New York, New York; 3Cancer Genetics Inc, Rutherford, New Jersey The cytogenetic alterations in renal oncocytoma (RO) are poorly understood. We analyzed 130 consecutive RO for karyotypic alterations. Clonal chromosome abnormalities were identified in 63 (48.5%) cases, which could be categorized into 3 classes of mutually exclusive cytogenetic categories. Class 1 RO had diploid karyotypes with 11q13 rearrangement in balanced translocations with ten or more different chromosome partners in all 20 (31.7%) cases. We identified recurrent translocation partners at 5q35, 6p21, 9p24, 11p13-14 and 11q23, and confirmed that CCND1 gene rearrangement at 11q13 utilizing fluorescence in situ hybridization (FISH). Class 2 RO exhibited hypodiploid karyotypes with loss of chromosome 1 and concurrent losses of Y in males and X in females in 25 (39.7%) cases. The class 3 tumors comprising of 18 (30.2%) cases showed diverse types of abnormalities with the involvement of 2 or more chromosomes exclusive of abnormalities seen in Class 1 and 2 tumors. Furthermore, karyotypically uninformative cases were subjected to FISH analysis to identify class 1 and 2 abnormalities. In this group we found similar frequencies of CCND1 rearrangement, loss of 1 or Y as with karyotypically abnormal cases. We validated our results against 91 tumors from the Mittleman database. Correlation of clinical data with all the 3 classes of RO showed no clear evidence of overall patient survival. Our findings support the hypothesis that RO exhibit 3 principal cytogenetic categories, which may have different roles in initiation and/or progression. These cytogenetic markers provide a key tool in the diagnostic evaluation of RO. Citation Format: Christopher B. Anderson, Michael Lipsky, Subhadra V. Nandula, Freeman E. Christopher, Matthews Thomas, Caitlin E. Walsh, Gen Li, Matthias Szabolcs, Mahesh M. Mansukhani, James M. McKiernan, Murty V. Vundavalli. Cytogenetics of renal oncocytomas identify three distinct and mutually exclusive diagnostic classes of chromosome aberrations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3415.

Although monosomy X is the most common karyotype in patients with Turner syndrome, the presence of Y chromosome material has been observed in about 10% of patients. Y chromosome material in patients with Turner syndrome poses an increased risk of gonadoblastoma and malignant transformation. We report a woman with a diagnosis of Turner syndrome at 12 years of age, without signs of virilization, and karyotype reported as 46,X,del(X)(q13). At 26 years, cytogenetic studies indicated the patient to be mosaic for monosomy X and a cell line that contained a du-plicated Yq chromosome. Bilateral gonadectomy was performed and revealed streak gonads, without evidence of gonadoblastoma. Histological analysis showed ovarian stromal cells with few primordial tubal structures. FISH performed on streak gonadal tissue showed a heterogeneous distribution of SRY, with exclusive localization to the primordial tubal structures. DNA extraction from the gonadal tissue showed a 6.5% prevalence of SRY by microarray analysis, contrasting the 86% prevalence in the peripheral blood sample. This indicates that the overall gonadal sex appears to be determined by the majority gonosome complement in gonadal tissue in cases of sex chromosome mosaicism. This case also raises questions regarding malignancy risk associated with Y prevalence and tubal structures in gonadal tissue.

Abstract The application of chromosomal microarray analysis (CMA) in cancer research has produced a wealth of useful information about copy number alterations (CNAs) and their implications in cancer classification, disease progression, therapy response, and patient outcome. However, only a handful of clinical laboratories are offering CMA for cancer diagnosis. This is largely due to the lack of effective diagnostic standards and guidelines for cancer applications, and the absence of a cancer microarray database to aid in post-analytic interpretation. We have designed a combined targeted-/whole-genome array specific for cancer using the microarray CGH format. Approximately 20,000 high quality oligonucleotide probes were selected from the Agilent Tech. (Santa Clara, CA) eArray system to target all exons and exon/intron boundaries of more than 500 cancer genes, over 100 known cancer-associated genomic regions and all subtelomeric chromosome regions. Intervals between aforementioned genes or regions were filled relatively evenly with oligonucleotide probes to cover the whole genome. Using this custom designed array, we studied 250 cases of hematological malignancies and 30 normal bone marrow or blood controls. In addition to confirming and clarifying cytogenetic and FISH results, the array revealed many previously unknown CNAs, including intra-gene deletions and duplications in patients with normal or abnormal karyotype. Many apparently balanced translocations were found to harbor cryptic CNAs at or near the breakpoints. Many CNAs displayed strong association with specific category of malignancies. GeneSpring Hierarchical Clustering analysis showed distinctive genomic signature patterns for different types or sub-types of haematological cancers. Using BlueFuse Multi software, we were able to create a few disease classification/decision tracks, which are of great clinical significance in post-analytic interpretation and genotype-phenotype correlation for cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 314. doi:10.1158/1538-7445.AM2011-314

The most frequent chromosomal rearrangement reported in acute promyelocytic leukemia （APL） is t（15;17）（q22;q21）. The t（15;17） generates the PML/RARA fusion gene that blocks the transcription of genes involved in myeloid cell differentiation. A small number of simple and complex variants of the classical t（15;17） have been reported. We report two complex three-way translocation variants,t（3;17;15）（q27;q21;q22） and t（8;17;15）（q24.3;q12;q22） in which the PML/RARA fusion gene has been created on the derivative 15 chromosomes. Many of these variant translocations are suspected by conventional cytogenetics but need to be confirmed with additional molecular testing. We discuss the importance of supplementing conventional cytogenetic testing with FISH and RT-PCR to accurately diagnose APL variant patients.