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A Role for BRCA1 in Uterine Leiomyosarcoma

Deyin Xing, George Scangas, Mai Nitta, Lei He, Xuan Xu, Yevgeniya J.M. Ioffe, Paul-Joseph Aspuria, Cyrus Y. Hedvat, Matthew L. Anderson, Esther Oliva, Beth Y. Karlan, Gayatry Mohapatra and Sandra Orsulic
Deyin Xing
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George Scangas
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Mai Nitta
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Lei He
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Xuan Xu
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Yevgeniya J.M. Ioffe
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Paul-Joseph Aspuria
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Cyrus Y. Hedvat
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Matthew L. Anderson
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Esther Oliva
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Beth Y. Karlan
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Gayatry Mohapatra
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Sandra Orsulic
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DOI: 10.1158/0008-5472.CAN-09-2543 Published November 2009
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    Figure 1.

    Characterization of uterine tumors in mice with conditional deletion of p53 and/or Brca1 using Amhr2-driven Cre recombinase. A, Kaplan-Meier survival curves for Amhr2Cre/+/Brca1lox/lox, Amhr2Cre/+/p53lox/lox, and Amhr2Cre/+/p53lox/lox/Brca1lox/lox mice. B, uterine tumors in Amhr2Cre/+/p53lox/lox (tumor 1) and Amhr2Cre/+/p53lox/lox/Brca1lox/lox mice (tumor 2). C, detection of Cre-mediated recombination of p53 in tumors dissected from an Amhr2Cre/+/p53lox/lox mouse (tumor 1) and double recombination of p53 and Brca1 in a tumor dissected from an Amhr2Cre/+/p53lox/lox/Brca1lox/lox mouse (tumor 2). Tail tissue from the Amhr2Cre/+/p53lox/lox/Brca1lox/lox mouse was used as a control.

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    Figure 2.

    Immunohistochemical analysis of normal uteri derived from Amhr2Cre/+/Brca1lox/lox mice and uterine tumors derived from Amhr2Cre/+/p53lox/lox and Amhr2Cre/+/p53lox/lox/Brca1lox/lox mice. Representative H&E staining (×100 and ×400 magnification). Incorporation of BrdUrd indicates a high proliferation index. The IHC profile shows that the myometrium of the uterus and the uterine tumors are positive for smooth muscle actin (SMA) but negative for the epithelial marker Keratin 8 (CK8). T, tumor; E, endometrium; M, myometrium; small arrow, abundant mitoses; large arrow, marked cytologic atypia; arrowhead, prominent nucleoli; *, hyperchromatic nuclei.

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    Figure 3.

    BRCA1 IHC and methylation status. A, representative immunohistochemical staining in BRCA1-negative ULMS, BRCA1-positive ULMS, and benign leiomyoma. B, methylation-specific PCR analysis of two BRCA1-negative (−) and six BRCA1-positive (+) samples. Sample 1, positive control for methylated BRCA1 promoter (ovary tumor in which methylation of the BRCA1 promoter has been previously shown); sample 2, negative control for methylated BRCA1 promoter (normal male DNA); samples 3 to 10, primary human ULMS samples in which the presence (+) or absence (−) of the BRCA1 protein has been determined by IHC. The IHC results are compared with the BRCA1 methylation status determined by methylation−specific PCR (MSP). M, methylated product; U, unmethylated product. Both methylated and unmethylated product size, 182 bp. *, an unmethylated product that is probably derived from stromal cells and connective tissues within the tumor.

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Cancer Research: 69 (21)
November 2009
Volume 69, Issue 21
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A Role for BRCA1 in Uterine Leiomyosarcoma
Deyin Xing, George Scangas, Mai Nitta, Lei He, Xuan Xu, Yevgeniya J.M. Ioffe, Paul-Joseph Aspuria, Cyrus Y. Hedvat, Matthew L. Anderson, Esther Oliva, Beth Y. Karlan, Gayatry Mohapatra and Sandra Orsulic
Cancer Res November 1 2009 (69) (21) 8231-8235; DOI: 10.1158/0008-5472.CAN-09-2543

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A Role for BRCA1 in Uterine Leiomyosarcoma
Deyin Xing, George Scangas, Mai Nitta, Lei He, Xuan Xu, Yevgeniya J.M. Ioffe, Paul-Joseph Aspuria, Cyrus Y. Hedvat, Matthew L. Anderson, Esther Oliva, Beth Y. Karlan, Gayatry Mohapatra and Sandra Orsulic
Cancer Res November 1 2009 (69) (21) 8231-8235; DOI: 10.1158/0008-5472.CAN-09-2543
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