Daniel Joseph Weisenberger

US Patent:

8642263, Feb 4, 2014

Filed:

Nov 10, 2005

Appl. No.:

11/719033

Inventors:

Peter W. Laird - South Pasadena CA, US
Daniel J. Weisenberger - Playa Del Rey CA, US
Mihaela Campan - Los Angeles CA, US
Tifany I. Long - Chino CA, US

Assignee:

University of Southern California - Los Angeles CA

International Classification:

C12Q 1/68

US Classification:

435 612, 435 61, 435 611

Abstract:

Preferred aspects provide novel high-throughput, sensitive methods (e. g. , real-time PCR-based (MethyLight™) reactions) for detection and/or measurement of global genomic 5-methylcytosine content, based on measurement of DNA methylation of Alu, LINE-1 repetitive sequences, and the chromosome 1 centromeric satellite alpha and juxtacentromeric satellite 2 repeat sequences. Additional aspects provide sensitive methods for determining the amount of a DNA (e. g. , in formalin-fixed, paraffin-embedded tissues). Combined (mean) use of Alu and Sat2 repeat methylation measurements provides for a surprisingly close correlation with global genomic 5-methylcytosine content measurements obtained by HPLC. Methylation of Alu repeats was determined to be closely associated with HPLC-based global methylation levels, as was methylation of satellite 2 and LINE-1 global genomic 5-methylcytosine content. The assays provide surrogate markers for global genomic 5-methylcytosine content analyzes, and have substantial utility for high-throughput and population-based studies (e. g.

US Patent:

20080254474, Oct 16, 2008

Filed:

Apr 14, 2008

Appl. No.:

12/102783

Inventors:

Peter W. Laird - South Pasadena CA, US
Binh N. Trinh - Alhambra CA, US
Mihaela Campan - Los Angeles CA, US
Daniel J. Weisenberger - Playa Del Rey CA, US

Assignee:

University of Southern California - Los Angeles CA

International Classification:

C12Q 1/68

US Classification:

435 6

Abstract:

Provided are novel sensitive methylation assays referred to herein as Digital MethyLight, comprising stochastically distributing and compartmentalizing bisulfite-treated genomic DNA over multiple PCR reaction wells for detection of individually methylated DNA molecules in a large background of unmethylated DNA. Digital Bisulfite Genomic DNA Sequencing methods are also provided for high-resolution DNA methylation information without subcloning. Background signal and PCR contaminants are diluted, while the ratio of primer to methylated template DNA is kept high. Preferably, biological fluid (e.g., urine, blood-based (e.g., plasma and/or serum)) samples are analyzed for cancer diagnosis, prognosis and surveillance. Multiplexed PCR formats may be implemented to enhance when using small DNA amounts. Compositions and methods for diagnosis and/or prognosis of breast cancer, comprising the use of FOXE1, CLDN5 and/or RUNX3 gene markers are also provided (SEQ ID NOS: 17, 16 and 18, respectively for respective CpG island sequences), and in preferred embodiments plasma or serum samples are used.

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:

20130065228, Mar 14, 2013

Filed:

Jun 1, 2012

Appl. No.:

13/486988

Inventors:

TOSHINORI HINOUE - ALHAMBRA CA, US
HUI SHEN - SAN GABRIEL CA, US
DANIEL J. WEISENBERGER - LOS ANGELES CA, US
PETER W. LAIRD - SOUTH PASADENA CA, US

Assignee:

UNIVERSITY OF SOUTHERN CALIFORNIA - LOS ANGELES CA

International Classification:

C12Q 1/68

US Classification:

435 611

Abstract:

Particular aspects provide methods and compositions (e.g., gene marker panels) having substantial utility for at least one of diagnosis, identification and classification of colorectal cancer (CRC) (e.g., tumors) relating to distinctive DNA methylation-based subgroups of CRC including CpG island methylator phenotype (CIMP) groups (e.g., CIMP-H and CIMP-L) and non-CIMP groups. Exemplary marker panels include: B3GAT2, FOXL2, KCNK13, RAB31 and SLIT1 (CIMP marker panel); and FAM78A, FSTL1, KCNC1, MYOCD, and SLC6A4 (CIMP-H marker panel). Further aspects relate to genetic mutations, and other epigenetic markers relating to said CRC subgroups that can be used in combination with the gene marker panels for at least one of diagnosis, identification and classification of colorectal cancer (CRC) (e.g., tumors) relating to distinctive CIMP and non-CIMP groups.

US Patent:

8110361, Feb 7, 2012

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. Weisenberger - Playa del Rey CA, US
Tiffany I. Long - Chino CA, US

Assignee:

University of Southern California USC Stevens Center for Innovation - Los Angeles CA

International Classification:

C12Q 1/68

US Classification:

435 614, 435 611, 435 612

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:

20160289768, Oct 6, 2016

Filed:

Mar 9, 2016

Appl. No.:

15/065782

Inventors:

- Los Angeles 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

International Classification:

C12Q 1/68

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).