Kimberly D Siegmund

US Patent:

8367336, Feb 5, 2013

Filed:

Jun 1, 2005

Appl. No.:

11/628390

Inventors:

Martin Widschwendter - Tonbridge, GB
Kimberly D. Siegmund - San Marino CA, US
Peter A. Jones - La Cañada CA, US
Peter W. Laird - South Pasadena CA, US

Assignee:

University of Southern California - Los Angeles CA

International Classification:

C12Q 1/68
C12P 19/34

US Classification:

435 611, 435 61, 435 612, 435 614, 435 618, 435 912

Abstract:

Particular embodiments provide novel and clinically useful DNA methylation predictors of hormone receptor status, and predictors of response to endocrine (e. g. , hormonal) and non-endocrine breast cancer therapy. The ESR1 gene, encoding the estrogen receptor (ER) alpha proved to be the preferred predictor of progesterone receptor (PR) status, while methylation of the PGR gene, encoding PR, was the preferred predictor of ER status. ESR1 methylation outperformed hormone receptor status as a predictor of clinical response in patients treated with antiestroges (e. g. , tamoxifen), while promoter methylation of the CYP1B1 gene, encoding a tamoxifen and estradiol metabolizing cytochrome P450, predicted response differentially in tamoxifen-treated and non-treated patients. High levels of promoter methylation of the ARH1 gene, encoding a RAS-related small G-protein, were shown to be preferred predictors of better survival in patients who had not received tamoxifen therapy.

US Patent:

20090053706, Feb 26, 2009

Filed:

May 2, 2006

Appl. No.:

11/913535

Inventors:

Peter W. Laird - South Pasadena CA, US
KImberly D. Siegmund - San Marino CA, US
Mihaela Campan - Los Angeles CA, US
Daniel J. Weisenberg - Playa del Rey CA, US
Tiffany I. Long - Chino CA, US

Assignee:

University of Southern California - Los Angles CA

International Classification:

C12Q 1/68
C12Q 1/02
G01N 33/53
C07H 21/00

US Classification:

435 6, 435 29, 435 71, 435 792, 536 2431

Abstract:

Particular aspects confirm the existence of a CpG island methylator phenotype (CIMP) in colorectal cancer, and provide novel validated DNA methylation markers associated with CIMP. Additional aspects provide novel methods and compositions for: determining CIMP status in colorectal cancers, determining the relationship between CIMP status and other molecular features of the cancers (e.g., BRAF mutation, KRAS mutation and MSI status); determining the relationship between CIMP status and other variables (e.g., age, sex, tumor location, family history, race, country of origin, tumor characteristics (including, tumor type, tumor grade, invasive margin characteristics, lymphocyte infiltration characteristics, direct spread, lymph node spread, venous spread and type of residual adjacent polyp, if present)); and determining, between subgroups defined by CIMP status and BRAF mutations, effects of selected risk factors (e.g., body mass index, smoking history, alcohol intake, dietary folate intake, folate metabolic enzyme polymorphisms and history of hormonal use).

US Patent:

20090246771, Oct 1, 2009

Filed:

Nov 3, 2008

Appl. No.:

12/264048

Inventors:

Peter W. Laird - South Pasadena CA, US
Sahar Houshdaran - Alhambra CA, US
Victoria Cortessis - Los Angeles CA, US
Kimberly D. Siegmund - San Marino CA, US
Rebecca Z. Sokol - Ventura CA, US

Assignee:

University of Southern California - Los Angeles CA

International Classification:

C12Q 1/68

US Classification:

435 6

Abstract:

Provided are compositions and methods for determining or diagnosing abnormal sperm or fertility, comprising: obtaining sperm DNA from a test subject; determining the methylation status of at least one CpG dinucleotide sequence of at least one gene sequence selected from HRAS, NTF3, MT1A, PAX8, DIRAS3, PLAGL1, SFN, SAT2CHRM1, MEST, RNR1, CYP27B1 and ICAM1; and thereby determining or diagnosing abnormal sperm or fertility. Provided are compositions and methods for identifying agents that cause spermatogenic deficits or abnormal sperm fertility, comprising: obtaining human ES-cell derived primordial germ cells; contacting the germ cells or descendants thereof, with a test agent; culturing the contacted cells; determining, using a genomic DNA of the sample, the methylation status of at least one CpG dinucleotide sequence of at least one gene sequence selected from the above group; and identifying at least one test agent that causes at least one of spermatogenic deficits, abnormal sperm, and abnormal fertility.

US Patent:

20100124747, May 20, 2010

Filed:

Nov 3, 2009

Appl. No.:

12/611309

Inventors:

Peter W. Laird - South Pasadena CA, US
Sahar Houshdaran - Alhambra CA, US
Victoria Cortessis - Los Angeles CA, US
Kimberly D. Siegmund - San Marino CA, US
Rebecca Z. Sokol - Ventura CA, US

Assignee:

University of Southern California - Los Angeles CA

International Classification:

C12Q 1/68

US Classification:

435 6

Abstract:

Provided are compositions and methods for diagnosis or prognosis of testicular or male germ-cell derived cancer, comprising: obtaining sperm DNA from a test subject; determining the methylation status of at least one CpG dinucleotide sequence of at least one gene sequence selected from HRAS, NTF3, MT1A, PAX8, DIRAS3, PLAGL1, SFN, SAT2CHRM1, MEST, RNR1, CYP27B1 and ICAM1; and thereby determining or diagnosing testicular or male germ-cell derived cancer. Provided are compositions and methods for identifying agents that cause testicular or male germ-cell derived cancer, comprising: obtaining human ES-cell derived primordial germ cells; contacting the germ cells or descendants thereof, with a test agent; culturing the contacted cells; determining, using a genomic DNA of the sample, the methylation status of at least one CpG dinucleotide sequence of at least one gene sequence selected from the above group; and identifying at least one test agent that causes testicular or male germ-cell derived cancer.

US Patent:

20120219946, Aug 30, 2012

Filed:

Feb 3, 2012

Appl. No.:

13/366192

Inventors:

Peter W. Laird - South Pasadena CA, US
Kimberly D. Siegmund - San Marino CA, US
Mihaela Campan - Los Angeles CA, US
Daniel J. Weisenberger - Playa del Rey CA, US
Tiffany I. Long - Chino CA, US

Assignee:

University of Southern California - Los Angeles CA

International Classification:

C12Q 1/68
C07H 21/04
G01N 33/574

US Classification:

435 611, 436501, 536 231

Abstract:

Particular aspects confirm the existence of a CpG island methylator phenotype (CIMP) in colorectal cancer, and provide novel validated DNA methylation markers associated with CIMP. Additional aspects provide novel methods and compositions for: determining CIMP status in colorectal cancers, determining the relationship between CIMP status and other molecular features of the cancers (e.g., BRAF mutation, KRAS mutation and MSI status); determining the relationship between CIMP status and other variables (e.g., age, sex, tumor location, family history, race, country of origin, tumor characteristics (including, tumor type, tumor grade, invasive margin characteristics, lymphocyte infiltration characteristics, direct spread, lymph node spread, venous spread and type of residual adjacent polyp, if present)); and determining, between subgroups defined by CIMP status and BRAF mutations, effects of selected risk factors (e.g., body mass index, smoking history, alcohol intake, dietary folate intake, folate metabolic enzyme polymorphisms and history of hormonal use).

US Patent:

20210404016, Dec 30, 2021

Filed:

Aug 11, 2021

Appl. No.:

17/399920

Inventors:

- Los Angeles CA, US
Jie Liu - San Mateo CA, US
Inderbir Singh Gill - Pasadena CA, US
Kimberly Siegmund - San Marino CA, US
Gangning Liang - Rowland Heights CA, US

International Classification:

C12Q 1/6886
G16H 50/50
G16H 50/20
C12Q 1/6827
C12Q 1/6858

Abstract:

A method of classifying kidney tumors is provided. The method includes obtaining a sample from a subject, isolating DNA from the sample, determining the methylation status of the DNA, and comparing the methylation status of the DNA to one or more methylated biomarkers selected from the following: cg04877910, cg09667289, cg05274650, cg11473616, cg16935734, cg27534624, cg21851713, cg15867829, cg15679829, cg08884979, cg09538401, cg26811868, cg05367028, cg19816080, cg20108357, cg25504868, cg11201447, cg19922137, cg14706317, cg15902830, cg10794973, cg10777887, cg03290131, cg07851269, cg11264947, cg00279406, cg23140965, cg03574652, cg03265671, cg24864241, cg01572891, cg00193963, cg14329285, cg17819990, cg17298239, cg23856138, cg21049501, cg11808936, cg25170591, cg17983632, cg08141142, cg19848599, cg25799109, cg07093324, cg16223546, cg07604732, cg12149606, cg08949329, cg27166177, cg26177041, cg09885851, cg22876153, cg21386992, cg02309772, cg02833180, cg20007890, cg04972244, cg02666955 and cg12102682. The comparison indicates whether the sample is clear cell malignant, papillary malignant, chromophobe malignant, angiomylolipomas (AML) benign, or oncocytoma benign.

US Patent:

20200347459, Nov 5, 2020

Filed:

Feb 24, 2020

Appl. No.:

16/799559

Inventors:

- Los Angeles CA, US
Gangning Liang - Los Angeles CA, US
Peter Jones - Los Angeles CA, US
Kimberly Siegmund - Los Angeles CA, US

International Classification:

C12Q 1/6886

Abstract:

A method for the prediction, prognosis and/or diagnosis of bladder cancer or bladder cancer recurrence in a subject, the method includes: providing a test sample from the subject; measuring DNA methylation levels of at least a portion of two or more polynucleotides selected from the group consisting of HOXA9, SOX1, NPY, IRAK3, L1-MET, and ZO2 in the test sample; calculating a risk score based on the measured DNA methylation levels, comparing the calculated risk score to a cut-off value derived from a reference DNA methylation profile based on DNA methylation levels of the one or more biomarkers derived from a control group, members of which had bladder cancer; and based on the comparison calculated risk score to the cut-off value, determining at least one of: (1) whether bladder cancer has recurred; (2) whether there is likelihood that the bladder cancer will recur; and (3) whether the patient has bladder cancer. The one or more polynucleotides preferably comprise SOX1, IRAK3 and L1-MET.

US Patent:

20190203303, Jul 4, 2019

Filed:

Jun 28, 2017

Appl. No.:

16/314335

Inventors:

Sameer Chopra - Los Angeles CA, US
Jie Liu - San Mateo CA, US
Inderbir Singh Gill - Pasadena CA, US
Kimberly Siegmund - San Marino CA, US

International Classification:

C12Q 1/6886
C12Q 1/6827
C12Q 1/6858
G16H 50/50
G16H 50/20

Abstract:

A method of classifying kidney tumors is provided. The method includes obtaining a sample from a subject, isolating DNA from the sample, determining the methylation status of the DNA, and comparing the methylation status of the DNA to one or more GO methylated biomarkers selected from the following: cg04877910, cg09667289, cg05274650, cg1 1473616, cg16935734, cg27534624, cg21851713, cg15867829, cg15679829, cg08884979, cg09538401, cg26811868, cg05367028, cg19816080, cg20108357, cg25504868, cg1 1201447, cg19922137, cg14706317, cg15902830, cg10794973, cg10777887, cg03290131, cg07851269, cg1 1264947, cg00279406, cg23140965, cg03574652, cg03265671, cg24864241, cg01572891, cg00193963, cg14329285, cg17819990, cg17298239, cg23856138, cg21049501, cg1 1808936, cg25170591, cg17983632, cg08141142, cg19848599, cg25799109, cg07093324, cg16223546, cg07604732, cg12149606, cg08949329, cg27166177, cg26177041, cg09885851, cg22876153, cg21386992, cg02309772, cg02833180, cg20007890, cg04972244, cg02666955 and cg12102682. The comparison indicates whether the sample is clear cell malignant, papillary malignant, chromophobe malignant, angiomylolipomas (AML) benign, or oncocytoma benign.