Person:
Dal Cin, Paola

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Dal Cin

First Name

Paola

Name

Dal Cin, Paola
Author's Publications: search.filters.isAuthorOfPublication.5a188492-3c4c-4678-b496-90647743e031

Search Results

Now showing 1 - 3 of 3
  • 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
    Refractory myeloid sarcoma with a FIP1L1-PDGFRA rearrangement detected by clinical high throughput somatic sequencing
    (BioMed Central, 2015) Mandelker, Diana; Dal Cin, Paola; Jacene, Heather; Armand, Philippe; Stone, Richard; Lindeman, Neal
    Next generation sequencing (NGS) is increasingly being used clinically to characterize the molecular alterations found in patients’ tumors. These testing results have the potential to affect clinical care by guiding therapeutic approaches based upon genotype. NGS based testing approaches have a distinct advantage over provider-ordered single gene testing in that they can detect unexpected, yet clinically important genetic changes. Here, we illustrate this principle with the case of a 33-year-old man with myeloid sarcoma that was refractory to six different chemotherapeutic regimens. Our clinical NGS assay detected an unanticipated FIP1L1-PDGFRA rearrangement in his tumor. The patient was immediately placed on Imatinib therapy to which he responded, and remains in remission 10 months after the rearrangement was initially detected.
  • No Thumbnail Available
    Publication
    Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma
    (American Association for Cancer Research (AACR), 2016-01-15) De Rienzo, Assunta; Archer, Michael A.; Yeap, Beow; Dao, Nhien; Sciaranghella, Daniele; Sideris, Antonios C.; Zheng, Yifan; Holman, Alexander G.; Wang, Yaoyu E.; Dal Cin, Paola; Fletcher, Jonathan; Rubio, Renee; Croft, Larry; Quackenbush, John; Sugarbaker, Peter E.; Munir, Kiara J.; Battilana, Jesse R.; Gustafson, Corinne; Chirieac, Lucian; Ching, Soo Meng; Wong, James; Tay, Liang Chung; Rudd, Stephen; Hercus, Robert; Sugarbaker, David J.; Richards, William; Bueno, Raphael
    Malignant pleural mesothelioma (MPM) is an aggressive cancer that occurs more frequently in men, but is associated with longer survival in women. Insight into the survival advantage of female patients may advance the molecular understanding of MPM and identify therapeutic interventions that will improve the prognosis for all MPM patients. In this study, we performed whole-genome sequencing of tumor specimens from 10 MPM patients and matched control samples to identify potential driver mutations underlying MPM. We identified molecular differences associated with gender and histology. Specifically, single-nucleotide variants of BAP1 were observed in 21% of cases, with lower mutation rates observed in sarcomatoid MPM (p<0.001). Chromosome 22q loss was more frequently associated with the epithelioid than that non-epitheliod histology (p=0.037), whereas CDKN2A deletions occurred more frequently in non-epithelioid subtypes among men (p=0.021) and were correlated with shorter overall survival for the entire cohort (p=0.002) and for men (p=0.012). Furthermore, women were more likely to harbor TP53 mutations (p=0.004). Novel mutations were found in genes associated with the integrin-linked kinase pathway, including MYH9 and RHOA. Moreover, expression levels of BAP1, MYH9, and RHOA were significantly higher in non-epithelioid tumors, and were associated with significant reduction in survival of the entire cohort and across gender subgroups. Collectively, our findings indicate that diverse mechanisms highly related to gender and histology appear to drive MPM.