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Expression of LINE-1 protein in human skin cancers [Meeting Abstract]
Zampella, JG; Cuda, JD; Burns, K
ISI:000380028800109
ISSN: 1523-1747
CID: 2673892
Nephrogenic systemic fibrosis: fibrotic plaques and contracture following exposure to gadolinium-based contrast media [Case Report]
He, Alice; Kwatra, Shawn G; Zampella, John G; Loss, Manisha J
PMCID:4840596
PMID: 27073153
ISSN: 1757-790x
CID: 2673802
A map of mobile DNA insertions in the NCI-60 human cancer cell panel
Zampella, John G; Rodic, Nemanja; Yang, Wan Rou; Huang, Cheng Ran Lisa; Welch, Jane; Gnanakkan, Veena P; Cornish, Toby C; Boeke, Jef D; Burns, Kathleen H
BACKGROUND: The National Cancer Institute-60 (NCI-60) cell lines are among the most widely used models of human cancer. They provide a platform to integrate DNA sequence information, epigenetic data, RNA and protein expression, and pharmacologic susceptibilities in studies of cancer cell biology. Genome-wide studies of the complete panel have included exome sequencing, karyotyping, and copy number analyses but have not targeted repetitive sequences. Interspersed repeats derived from mobile DNAs are a significant source of heritable genetic variation, and insertions of active elements can occur somatically in malignancy. METHOD: We used Transposon Insertion Profiling by microarray (TIP-chip) to map Long INterspersed Element-1 (LINE-1, L1) and Alu Short INterspersed Element (SINE) insertions in cancer genes in NCI-60 cells. We focused this discovery effort on annotated Cancer Gene Index loci. RESULTS: We catalogued a total of 749 and 2,100 loci corresponding to candidate LINE-1 and Alu insertion sites, respectively. As expected, these numbers encompass previously known insertions, polymorphisms shared in unrelated tumor cell lines, as well as unique, potentially tumor-specific insertions. We also conducted association analyses relating individual insertions to a variety of cellular phenotypes. CONCLUSIONS: These data provide a resource for investigators with interests in specific cancer gene loci or mobile element insertion effects more broadly. Our data underscore that significant genetic variation in cancer genomes is owed to LINE-1 and Alu retrotransposons. Our findings also indicate that as large numbers of cancer genomes become available, it will be possible to associate individual transposable element insertion variants with molecular and phenotypic features of these malignancies.
PMCID:5087121
PMID: 27807467
ISSN: 1759-8753
CID: 2303532
Diagnostic utility of 5-hydroxymethylcytosine immunohistochemistry in melanocytic proliferations
Rodic, Nemanja; Zampella, John; Sharma, Reema; Burns, Kathleen H; Taube, Janis M
Decreased hydroxymethylated cytosine (5-hydroxymethycytosine, 5-hmC) is reported to correlate with melanocyte dysplasia. The purpose of this study was to assess the diagnostic utility of this observation. 5-hmC immunohistochemistry was performed on tissue microarrays containing 171-melanocytic lesions from two different institutions. An immunohistochemical staining score representing the percentage and intensity of nuclear staining was assigned. The performance characteristics of 5-hmC immunohistochemistry for discriminating between a nevus and melanoma were determined. Additional cases of melanoma arising in a nevus (n = 8), nodal nevi (n = 5) and melanoma micrometastases to a lymph node (n = 6) were also assessed. Pronounced 5-hmC loss was observed in melanomas when compared with nevi (mean +/- standard deviation = 6.71 +/- 11.78 and 55.19 +/- 23.66, respectively, p < 0.0001). While the mean immunohistochemical staining score values for melanocytic nevi and melanoma were distinct, there was considerable variability in immunohistochemical staining score within a single diagnostic category. The sensitivity and specificity of this assay for nevus vs. melanoma is 92.74 and 97.78%, respectively. Distinct biphasic staining patterns were observed in cases of melanoma arising in association with a nevus. Relative changes of 5-hmC expression within a single lesion may be more informative than absolute values when using 5-hmC as a diagnostic adjunct.
PMCID:4715679
PMID: 26239102
ISSN: 1600-0560
CID: 2673842
Racial differences in the use of extracorporeal photopheresis for mycosis fungoides
Agi, Crystal; Kuhn, Diane; Chung, Jina; Zampella, John; Hinds, Ginette
BACKGROUND: Extracorporeal photopheresis (ECP) is an effective treatment option for mycosis fungoides (MF) and associated with few systemic side effects. OBJECTIVE: We sought to investigate whether there were differences in rates of ECP use between African-American and Caucasian patients with stage III/IV MF. METHODS: We conducted a retrospective review of all patients treated for MF at the Johns Hopkins Hospital main campus outpatient clinic between 1999 and 2011. RESULTS: We identified 65 patients with stage III or IV disease, 20 African-American and 45 Caucasian. Only 7 of 20 African-American patients (35%) compared with 30 of 45 (66%) of Caucasian patients were treated with ECP (p = 0.029). In addition, ECP was discussed as an option for 45% of African-Americans compared to 82% of Caucasians (p = 0.007). When discussed as an option, African-Americans and Caucasians had identical rates of ECP use (78% vs 81%, p = 0.841). CONCLUSIONS: Differences in rates of ECP use exist among African-American patients when compared to their Caucasian counterparts and may be related to how often ECP is offered as a treatment option. Improving physician awareness of the factors that influence treatment decision making may help diminish discrepancies in treatment regimens among patients with MF.
PMID: 25034002
ISSN: 1471-1753
CID: 2673862
Mycosis Fungoides and Variants: Board Review [Editorial]
Wheat, Chikoti M; Zampella, John; Kwatra, Shawn G; Jourabchi, Natanel; Okoye, Ginette A
ISI:000349202500015
ISSN: 1545-9616
CID: 2726612
Early-onset mycosis fungoides among African American women: a single-institution study
Balagula, Yevgeniy; Dusza, Stephen W; Zampella, John; Sweren, Ronald; Hinds, Ginette A
PMID: 25128117
ISSN: 1097-6787
CID: 2673852
The presence of T-cell clonality at presentation with mycosis fungoides is not influenced by patient gender or age [Meeting Abstract]
Balagula, Y; Dusza, S; Zampella, JG; Sweren, R; Hinds, GA
ISI:000334560400298
ISSN: 1523-1747
CID: 2673882
Long Interspersed Element-1 Protein Expression Is a Hallmark of Many Human Cancers
Rodic, Nemanja; Sharma, Reema; Sharma, Rajni; Zampella, John; Dai, Lixin; Taylor, Martin S; Hruban, Ralph H; Iacobuzio-Donahue, Christine A; Maitra, Anirban; Torbenson, Michael S; Goggins, Michael; Shih, Ie-Ming; Duffield, Amy S; Montgomery, Elizabeth A; Gabrielson, Edward; Netto, George J; Lotan, Tamara L; De Marzo, Angelo M; Westra, William; Binder, Zev A; Orr, Brent A; Gallia, Gary L; Eberhart, Charles G; Boeke, Jef D; Harris, Chris R; Burns, Kathleen H
Cancers comprise a heterogeneous group of human diseases. Unifying characteristics include unchecked abilities of tumor cells to proliferate and spread anatomically, and the presence of clonal advantageous genetic changes. However, universal and highly specific tumor markers are unknown. Herein, we report widespread long interspersed element-1 (LINE-1) repeat expression in human cancers. We show that nearly half of all human cancers are immunoreactive for a LINE-1-encoded protein. LINE-1 protein expression is a common feature of many types of high-grade malignant cancers, is rarely detected in early stages of tumorigenesis, and is absent from normal somatic tissues. Studies have shown that LINE-1 contributes to genetic changes in cancers, with somatic LINE-1 insertions seen in selected types of human cancers, particularly colon cancer. We sought to correlate this observation with expression of the LINE-1-encoded protein, open reading frame 1 protein, and found that LINE-1 open reading frame 1 protein is a surprisingly broad, yet highly tumor-specific, antigen.
PMCID:4005969
PMID: 24607009
ISSN: 0002-9440
CID: 886902
DIFFUSE REDUCTIONOF 5-HYDROXYMETHYLCYTOSINE MARKS VASTMAJORITY OF MALIGNANT MELANOMAS [Meeting Abstract]
Rodic, Nemanja; Zampella, John; Taube, Janis; Burns, Kathleen
ORIGINAL:0012280
ISSN: 1471-1753
CID: 2726652