Person:
Morton, Cynthia

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Morton

First Name

Cynthia

Name

Morton, Cynthia

Filters

2012 - 201814

Settings

Author's Publications: search.filters.isAuthorOfPublication.3ccab264-6c11-4fee-85d1-ec8a1d462106

Search Results

Now showing 1 - 10 of 14
  • Thumbnail Image
    Publication
    Intravenous Leiomyomatosis: An Unusual Intermediate between Benign and Malignant Uterine Smooth Muscle Tumors
    (2016) Ordulu, Zehra; Nucci, Marisa; Dal Cin, Paola; Hollowell, Monica; Otis, Christopher N.; Hornick, Jason; Park, Peter; Kim, Tae-Min; Quade, Bradley; Morton, Cynthia
    Intravenous leiomyomatosis is an unusual smooth muscle neoplasm with quasi-malignant intravascular growth but a histologically banal appearance. Herein, we report expression and molecular cytogenetic analyses of a series of 12 intravenous leiomyomatosis cases to understand better the pathogenesis of intravenous leiomyomatosis. All cases were analyzed for expression of HMGA2, MDM2 and CDK4 proteins by immunohistochemistry based on our previous finding of der(14)t(12;14)(q14.3;q24) in intravenous leiomyomatosis. Seven of 12 (58%) intravenous leiomyomatosis cases expressed HMGA2, and none expressed MDM2 or CDK4. Co-localization of hybridization signals for probes from the HMGA2 locus (12q14.3) and from 14q24 by interphase fluorescence in situ hybridization (FISH) was detected in a mean of 89.2% of nuclei in HMGA2-positive cases by immunohistochemistry, but in only 12.4% of nuclei in negative cases, indicating an association of HMGA2 expression and this chromosomal rearrangement (p=8.24×10−10). Four HMGA2-positive cases had greater than two HMGA2 hybridization signals per cell. No cases showed loss of a hybridization signal by interphase FISH for the frequently deleted region of 7q22 in uterine leiomyomata. One intravenous leiomyomatosis case analyzed by array comparative genomic hybridization revealed complex copy number variations. Finally, expression profiling was performed on three intravenous leiomyomatosis cases. Interestingly, hierarchical cluster analysis of the expression profiles revealed segregation of the intravenous leiomyomatosis cases with leiomyosarcoma rather than with myometrium, uterine leiomyoma of the usual histological type, or plexiform leiomyoma. These findings suggest that intravenous leiomyomatosis cases share some molecular cytogenetic characteristics with uterine leiomyoma, and expression profiles similar to that of leiomyosarcoma cases, further supporting their intermediate, quasi-malignant behavior.
  • Thumbnail Image
    Publication
    Pelvic and pulmonary benign metastasizing leiomyoma: A case report
    (Elsevier, 2018) Bakkensen, Jennifer; Samore, Wesley; Bortoletto, Pietro; Morton, Cynthia; Anchan, Raymond
    Seven years after she had a total abdominal hysterectomy for benign leiomyomas, a 46-year-old woman presented with a pelvic mass and multiple pulmonary nodules. She underwent resection of the mass and core needle biopsy of a pulmonary lesion. Histopathologic analysis revealed that both the pelvic and the pulmonary lesions were consistent with benign leiomyomas. Benign metastasizing leiomyoma should be considered if a woman of reproductive age and with a history of leiomyomas presents with extrauterine nodules without evidence of malignancy. The final diagnosis should be based on histopathological examination. Treatment depends on tumor size, location, receptor positivity, and disease progression.
  • Thumbnail Image
    Publication
    Identification of Balanced Chromosomal Rearrangements Previously Unknown Among Participants in the 1000 Genomes Project: Implications for Interpretation of Structural Variation in Genomes and the Future of Clinical Cytogenetics
    (2017) Dong, Zirui; Wang, Huilin; Chen, Haixiao; Jiang, Hui; Yuan, Jianying; Yang, Zhenjun; Wang, Wen-Jing; Xu, Fengping; Guo, Xiaosen; Cao, Ye; Zhu, Zhenzhen; Geng, Chunyu; Cheung, Wan Chee; Kwok, Yvonne K; Yang, Huangming; Leung, Tak Yeung; Morton, Cynthia; Cheung, Sau Wai; Choy, Kwong Wai
    Purpose Recent studies demonstrate that whole-genome sequencing (WGS) enables detection of cryptic rearrangements in apparently balanced chromosomal rearrangements (also known as balanced chromosomal abnormalities, BCAs) previously identified by conventional cytogenetic methods. We aimed to assess our analytical tool for detecting BCAs in The 1000 Genomes Project without knowing affected bands. Methods: The 1000 Genomes Project provides an unprecedented integrated map of structural variants in phenotypically normal subjects, but there is no information on potential inclusion of subjects with apparently BCAs akin to those traditionally detected in diagnostic cytogenetics laboratories. We applied our analytical tool to 1,166 genomes from the 1000 Genomes Project with sufficient physical coverage (8.25-fold). Results: Our approach detected four reciprocal balanced translocations and four inversions ranging in size from 57.9 kb to 13.3 Mb, all of which were confirmed by cytogenetic methods and PCR studies. One of DNAs has a subtle translocation that is not readily identified by chromosome analysis due to similar banding patterns and size of exchanged segments, and another results in disruption of all transcripts of an OMIM gene. Conclusions: Our study demonstrates the extension of utilizing low-coverage WGS for unbiased detection of BCAs including translocations and inversions previously unknown in the 1000 Genomes Project.
  • Thumbnail Image
    Publication
    A multi-stage genome-wide association study of uterine fibroids in African Americans
    (Springer Berlin Heidelberg, 2017) Hellwege, Jacklyn N.; Jeff, Janina M.; Wise, Lauren A.; Gallagher, C. Scott; Wellons, Melissa; Hartmann, Katherine E.; Jones, Sarah F.; Torstenson, Eric S.; Dickinson, Scott; Ruiz-Narváez, Edward A.; Rohland, Nadin; Allen, Alexander; Reich, David; Tandon, Arti; Pasaniuc, Bogdan; Mancuso, Nicholas; Im, Hae Kyung; Hinds, David A.; Palmer, Julie R.; Rosenberg, Lynn; Denny, Joshua C.; Roden, Dan M.; Stewart, Elizabeth A.; Morton, Cynthia; Kenny, Eimear E.; Edwards, Todd L.; Velez Edwards, Digna R.
    Uterine fibroids are benign tumors of the uterus affecting up to 77% of women by menopause. They are the leading indication for hysterectomy, and account for $34 billion annually in the United States. Race/ethnicity and age are the strongest known risk factors. African American (AA) women have higher prevalence, earlier onset, and larger and more numerous fibroids than European American women. We conducted a multi-stage genome-wide association study (GWAS) of fibroid risk among AA women followed by in silico genetically predicted gene expression profiling of top hits. In Stage 1, cases and controls were confirmed by pelvic imaging, genotyped and imputed to 1000 Genomes. Stage 2 used self-reported fibroid and GWAS data from 23andMe, Inc. and the Black Women’s Health Study. Associations with fibroid risk were modeled using logistic regression adjusted for principal components, followed by meta-analysis of results. We observed a significant association among 3399 AA cases and 4764 AA controls at rs739187 (risk-allele frequency = 0.27) in CYTH4 (OR (95% confidence interval) = 1.23 (1.16–1.30), p value = 7.82 × 10−9). Evaluation of the genetic association results with MetaXcan identified lower predicted gene expression of CYTH4 in thyroid tissue as significantly associated with fibroid risk (p value = 5.86 × 10−8). In this first multi-stage GWAS for fibroids among AA women, we identified a novel risk locus for fibroids within CYTH4 that impacts gene expression in thyroid and has potential biological relevance for fibroids. Electronic supplementary material The online version of this article (doi:10.1007/s00439-017-1836-1) contains supplementary material, which is available to authorized users.
  • Thumbnail Image
    Publication
    Identification and function of long non-coding RNA
    (Frontiers Media S.A., 2013) Ernst, Carl; Morton, Cynthia
    Long non-coding (lnc) RNAs are defined as non-protein coding RNAs distinct from housekeeping RNAs such as tRNAs, rRNAs, and snRNAs, and independent from small RNAs with specific molecular processing machinery such as micro- or piwi-RNAs. Recent studies of lncRNAs across different species have revealed a diverse population of RNA molecules of differing size and function. RNA sequencing studies suggest transcription throughout the genome, so there is a need to understand how sequence relates to functional and structural relationships amongst RNA molecules. Our synthesis of recent studies suggests that neither size, presence of a poly-A tail, splicing, direction of transcription, nor strand specificity are of importance to lncRNA function. Rather, relative genomic position in relation to a target is fundamentally important. In this review, we describe issues of key importance in functional assessment of lncRNA and how this might apply to lncRNAs important in neurodevelopment.
  • Thumbnail Image
    Publication
    Using population admixture to help complete maps of the human genome
    (2013) Genovese, Giulio; Handsaker, Robert; Li, Heng; Altemose, Nicolas; Lindgren, Amelia M.; Chambert, Kimberly; Pasaniuc, Bogdan; Price, Alkes; Reich, David; Morton, Cynthia; Pollak, Martin; Wilson, James G.; McCarroll, Steven
    Tens of millions of base pairs of euchromatic human genome sequence, including many protein-coding genes, have no known location in the human genome. We describe an approach for localizing the human genome's missing pieces by utilizing the patterns of genome sequence variation created by population admixture. We mapped the locations of 70 scaffolds spanning four million base pairs of the human genome's unplaced euchromatic sequence, including more than a dozen protein-coding genes, and identified eight large novel inter-chromosomal segmental duplications. We find that most of these sequences are hidden in the genome's heterochromatin, particularly its pericentromeric regions. Many cryptic, pericentromeric genes are expressed in RNA and have been maintained intact for millions of years while their expression patterns diverged from those of paralogous genes elsewhere in the genome. We describe how knowledge of the locations of these sequences can inform disease association and genome biology studies.
  • Thumbnail Image
    Publication
    Complex cytogenetic rearrangements at the DURS1 locus in syndromic Duane retraction syndrome
    (Blackwell Publishing Ltd, 2013) Baris, Hagit N; Chan, Wai-Man; Andrews, Caroline; Behar, Doron M; Donovan, Diana J; Morton, Cynthia; Ranells, Judith; Pal, Tuya; Ligon, Azra; Engle, Elizabeth
    Key Clinical Message A patient with syndromic Duane retraction syndrome harbors a chromosome 811.1q13.2 inversion and 8p11.1-q12.3 marker chromosome containing subregions with differing mosaicism and allele frequencies. This case highlights the potential requirement for multiple genetic methods to gain insight into genotype–phenotype correlation, and ultimately into molecular mechanisms that underlie human disease.
  • Thumbnail Image
    Publication
    Spectrum of genes involved in a unique case of Potocki Schaffer syndrome with a large chromosome 11 deletion
    (Dustri-Verlag Dr. Karl Feistle, 2014) Romeike, Bernd F.M.; Shen, Yiping; Nishimoto, Hiromi Koso; Morton, Cynthia; Layman, Lawrence C.; Kim, Hyung-Goo
    Letter to the Editor.
  • Thumbnail Image
    Publication
    Training the Future Leaders in Personalized Medicine
    (MDPI, 2016) Mason-Suares, Heather; Sweetser, David; Lindeman, Neal; Morton, Cynthia
    The era of personalized medicine has arrived, and with it a need for leaders in this discipline. This generation of trainees requires a cadre of new skill sets to lead the implementation of personalized medicine into mainstream healthcare. Traditional training programs no longer provide trainees with all the skills they will need to optimize implementation of this revolution now underway in medicine. Today’s trainees must manage clinical teams, act as clinical and molecular diagnostic consultants, train other healthcare professionals, teach future generations, and be knowledgeable about clinical trials to facilitate genomic-based therapies. To prepare trainees for the transition to junior faculty positions, contemporary genomic training programs must emphasize the development of these management, teaching, and clinical skills.
  • Thumbnail Image
    Publication
    Screening of deafness-causing DNA variants that are common in patients of European ancestry using a microarray-based approach
    (Public Library of Science, 2017) Yan, Denise; Xiang, Guangxin; Chai, Xingping; Qing, Jie; Shang, Haiqiong; Zou, Bing; Mittal, Rahul; Shen, Jun; Smith, Richard J. H.; Fan, Yao-Shan; Blanton, Susan H.; Tekin, Mustafa; Morton, Cynthia; Xing, Wanli; Cheng, Jing; Liu, Xue Zhong
    The unparalleled heterogeneity in genetic causes of hearing loss along with remarkable differences in prevalence of causative variants among ethnic groups makes single gene tests technically inefficient. Although hundreds of genes have been reported to be associated with nonsyndromic hearing loss (NSHL), GJB2, GJB6, SLC26A4, and mitochondrial (mt) MT-RNR1 and MTTS are the major contributors. In order to provide a faster, more comprehensive and cost effective assay, we constructed a DNA fluidic array, CapitalBioMiamiOtoArray, for the detection of sequence variants in five genes that are common in most populations of European descent. They consist of c.35delG, p.W44C, p.L90P, c.167delT (GJB2); 309kb deletion (GJB6); p.L236P, p.T416P (SLC26A4); and m.1555A>G, m.7444G>A (mtDNA). We have validated our hearing loss array by analyzing a total of 160 DNAs samples. Our results show 100% concordance between the fluidic array biochip-based approach and the established Sanger sequencing method, thus proving its robustness and reliability at a relatively low cost.