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  1. Article ; Online: Comparative genomics of high grade neuroendocrine carcinoma of the cervix.

    R Tyler Hillman / Robert Cardnell / Junya Fujimoto / Won-Chul Lee / Jianjun Zhang / Lauren A Byers / Preetha Ramalingam / Mario Leitao / Elizabeth Swisher / P Andrew Futreal / Michael Frumovitz

    PLoS ONE, Vol 15, Iss 6, p e

    2020  Volume 0234505

    Abstract: In order to improve treatment selection for high grade neuroendocrine carcinomas of the cervix (NECC), we performed a comparative genomic analysis between this rare tumor type and other cervical cancer types, as well as extra-cervical neuroendocrine ... ...

    Abstract In order to improve treatment selection for high grade neuroendocrine carcinomas of the cervix (NECC), we performed a comparative genomic analysis between this rare tumor type and other cervical cancer types, as well as extra-cervical neuroendocrine small cell carcinomas of the lung and bladder. We performed whole exome sequencing on fresh-frozen tissue from 15 NECCs and matched normal tissue. We then identified mutations and copy number variants using standard analysis pipelines. Published mutation tables from cervical cancers and extra-cervical small cell carcinomas were used for comparative analysis. Descriptive statistical methods were used and a two-sided threshold of P < .05 was used for significance. In the NECC cohort, we detected a median of 1.7 somatic mutations per megabase (range 1.0-20.9). PIK3CA p.E545K mutations were the most frequency observed oncogenic mutation (4/15 tumors, 27%). Activating MAPK pathway mutations in KRAS (p.G12D) and GNAS (p.R201C) co-occurred in two tumors (13%). In total we identified PI3-kinase or MAPK pathway activating mutations in 67% of NECC. When compared to NECC, lung and bladder small cell carcinomas exhibited a statistically significant higher rate of coding mutations (P < .001 for lung; P = .001 for bladder). Mutation of TP53 was uncommon in NECC (13%) and was more frequent in both lung (103 of 110 tumors [94%], P < .001) and bladder (18 of 19 tumors [95%], P < .001) small cell carcinoma. These comparative genomics data suggest that NECC may be genetically more similar to common cervical cancer subtypes than to extra-cervical small cell neuroendocrine carcinomas of the lung and bladder. These results may have implications for the selection of cytotoxic and targeted therapy regimens for this rare disease.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Barriers Prevent Patient Access to Personalized Therapies Identified by Molecular Tumor Profiling of Gynecologic Malignancies

    R. Tyler Hillman / Kristy Ward / Cheryl Saenz / Michael McHale / Steven Plaxe

    Journal of Personalized Medicine, Vol 5, Iss 2, Pp 165-

    2015  Volume 173

    Abstract: Objective. This study was designed to evaluate the ability of commercial molecular tumor profiling to discover actionable mutations and to identify barriers that might prevent patient access to personalized therapies. Methods. We conducted an IRB- ... ...

    Abstract Objective. This study was designed to evaluate the ability of commercial molecular tumor profiling to discover actionable mutations and to identify barriers that might prevent patient access to personalized therapies. Methods. We conducted an IRB-approved retrospective review of 26 patients with gynecologic malignancies who underwent commercial tumor profiling at our institution during the first 18 months of test availability. Tumor profiles reported targeted therapies and clinical trials matched to patient-specific mutations. Data analysis consisted of descriptive statistics. Results. Most patients who underwent tumor profiling had serous epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (46%). Patients underwent profiling after undergoing a median of two systemic therapies (range 0 to 13). A median of one targeted therapy was suggested per patient profile. Tumor profiling identified no clinically actionable mutations for seven patients (27%). Six patients sought insurance approval for a targeted therapy and two were declined (33%). One patient (4%) received a targeted therapy and this was discontinued due to tumor progression. Conclusions. There are formidable barriers to targeted therapy for patients with gynecologic malignancies. These barriers include a dearth of FDA-approved targeted agents for gynecologic malignancies, lack of third party insurance coverage and limited geographic availability of clinical trials.
    Keywords targeted therapies ; tumor markers ; genetics ; molecular biology ; next generation sequencing ; Medicine ; R
    Subject code 616 ; 610
    Language English
    Publishing date 2015-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: HPV-related anal cancer is associated with changes in the anorectal microbiome during cancer development

    Jacob H. Elnaggar / Victoria O. Huynh / Daniel Lin / R. Tyler Hillman / Chike O. Abana / Molly B. El Alam / Katarina C. Tomasic / Tatiana V. Karpinets / Ramez Kouzy / Jae L. Phan / Jennifer Wargo / Emma B. Holliday / Prajnan Das / Melissa P. Mezzari / Nadim J. Ajami / Erica J. Lynn / Bruce D. Minsky / Van K. Morris / Andrea Milbourne /
    Craig A. Messick / Ann H. Klopp / P. Andrew Futreal / Cullen M. Taniguchi / Kathleen M. Schmeler / Lauren E. Colbert

    Frontiers in Immunology, Vol

    2023  Volume 14

    Abstract: BackgroundSquamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less ... ...

    Abstract BackgroundSquamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease.MethodsPatients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade lower genital tract dysplasia. Anorectal tumor swabs were prospectively collected from patients with biopsy-confirmed locally advanced SCCA prior to receiving standard-of-care chemoradiotherapy (CRT). Patients with high-grade lower genital tract dysplasia without anal dysplasia were considered high-risk (HR Normal). 16S V4 rRNA Microbiome sequencing was performed for anal swabs. Alpha and Beta Diversity and composition were compared for HR Normal, anal dysplasia, and anal cancer.Results60 patients with high-grade lower genital tract dysplasia were initially enrolled. Seven patients had concurrent anal dysplasia and 44 patients were considered HR Normal. Anorectal swabs from 21 patients with localized SCCA were included, sequenced, and analyzed in the study. Analysis of weighted and unweighted UniFrac distances demonstrated significant differences in microbial community composition between anal cancer and HR normal (p=0.018). LEfSe identified that all three groups exhibited differential enrichment of specific taxa. Peptoniphilus (p=0.028), Fusobacteria (p=0.0295), Porphyromonas (p=0.034), and Prevotella (p=0.029) were enriched in anal cancer specimens when compared to HR normal.ConclusionAlthough alpha diversity was similar between HR Normal, dysplasia and cancer patients, composition differed significantly between the three groups. Increased ...
    Keywords anal cancer ; anorectal microbiome ; HPV-related cancer ; anal dysplasia ; cancer biology ; Immunologic diseases. Allergy ; RC581-607
    Subject code 610
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: KMT2D/MLL2 inactivation is associated with recurrence in adult-type granulosa cell tumors of the ovary

    R. Tyler Hillman / Joseph Celestino / Christopher Terranova / Hannah C. Beird / Curtis Gumbs / Latasha Little / Tri Nguyen / Rebecca Thornton / Samantha Tippen / Jianhua Zhang / Karen H. Lu / David M. Gershenson / Kunal Rai / Russell R. Broaddus / P. Andrew Futreal

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 7

    Abstract: Adult-type granulosa cell tumors of the ovary (aGCTs) are rare and recurrence is difficult to treat. Here, the authors observe in aGCT a novel recurrent somatic truncating mutation of KMT2D, more frequent in recurrent aGCT, and also non-genetic loss of ... ...

    Abstract Adult-type granulosa cell tumors of the ovary (aGCTs) are rare and recurrence is difficult to treat. Here, the authors observe in aGCT a novel recurrent somatic truncating mutation of KMT2D, more frequent in recurrent aGCT, and also non-genetic loss of KMT2D expression.
    Keywords Science ; Q
    Language English
    Publishing date 2018-06-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: KMT2D/MLL2 inactivation is associated with recurrence in adult-type granulosa cell tumors of the ovary

    R. Tyler Hillman / Joseph Celestino / Christopher Terranova / Hannah C. Beird / Curtis Gumbs / Latasha Little / Tri Nguyen / Rebecca Thornton / Samantha Tippen / Jianhua Zhang / Karen H. Lu / David M. Gershenson / Kunal Rai / Russell R. Broaddus / P. Andrew Futreal

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 7

    Abstract: Adult-type granulosa cell tumors of the ovary (aGCTs) are rare and recurrence is difficult to treat. Here, the authors observe in aGCT a novel recurrent somatic truncating mutation of KMT2D, more frequent in recurrent aGCT, and also non-genetic loss of ... ...

    Abstract Adult-type granulosa cell tumors of the ovary (aGCTs) are rare and recurrence is difficult to treat. Here, the authors observe in aGCT a novel recurrent somatic truncating mutation of KMT2D, more frequent in recurrent aGCT, and also non-genetic loss of KMT2D expression.
    Keywords Science ; Q
    Language English
    Publishing date 2018-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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