GENE METHYLATION IN THYROID CANCER DIAGNOSIS

• US 20090075265A1
• Filed: 02/01/2008
• Published: 03/19/2009
• Est. Priority Date: 02/02/2007
• Status: Abandoned Application

• Current Assignee: Orion Genomics LLC
• Original Assignee: Orion Genomics LLC
• Inventors: BUDIMAN, MUHAMMAD A., JEDDELOH, JEFFREY A., KORSHUNOVA, YULIA, MALONEY, REBECCA
• Application Number:
  US12/024,769
• Publication Number:
  US 20090075265A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/154 Methylation markers

Abstract

The present invention provides DNA biomarker sequences that are differentially methylated in samples from normal individuals and individuals with thyroid cancer. The invention further provides methods of identifying differentially methylated DNA biomarker sequences and their use the detection and diagnosis of thyroid cancer.

Claims

1. A method for determining the presence or absence of thyroid cancer in an individual, the method comprising:

a) determining the methylation status of at least one cytosine within a DNA region in a sample from the individual where the DNA region is at least 90% identical to a sequence selected from the group consisting of SEQ ID NO;

436, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, and 485;

b) comparing the methylation status of the at least one cytosine to a threshold value for the at least one cytosine, wherein the threshold value distinguishes between individuals with and without thyroid cancer, wherein the comparison of the methylation status to the threshold value is predictive of the presence or absence of thyroid cancer in the individual.

2. The method of claim 1, wherein the determining step comprises determining the methylation status of at least one cytosine in the DNA region corresponding to a nucleotide in a biomarker, wherein the biomarker is at least 90% identical to a sequence selected from the group consisting of SEQ ID NO:

292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, and 388.

3. The method of claim 2, wherein the determining step comprises determining the methylation status of the DNA region corresponding to the biomarker.

4. The method of claim 1, wherein the sample is from blood serum, blood plasma, or a biopsy.

5. The method of claim 1, wherein the methylation status of at least one biomarker from the list is compared to the methylation value of a control locus.

6. The method of claim 5, wherein the control locus is an endogenous control.

7. The method of claim 5, wherein the control locus is an exogenous control.

8. The method of claim 1, wherein the determining step comprises determining the methylation status of at least one cytosine from at least two DNA regions.

9. A computer-implemented method for determining the presence or absence of thyroid cancer in an individual, the method comprising:

receiving, at a host computer, a methylation value representing the methylation status of at least one cytosine within a DNA region in a sample from the individual where the DNA region is at least 90% identical to a sequence selected from the group consisting of SEQ ID NO;

436, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, and 485; and

comparing, in the host computer, the methylation value to a threshold value, wherein the threshold value distinguishes between individuals with and without thyroid cancer, wherein the comparison of the methylation value to the threshold value is predictive of the presence or absence of thyroid cancer in the individual.

10. The method of claim 9, wherein the receiving step comprises receiving at least two methylation values, the two methylation values representing the methylation status of at least one cytosine biomarkers from two different DNA regions;

and

the comparing step comprises comparing the methylation values to one or more threshold value(s) wherein the threshold value distinguishes between individuals with and without thyroid cancer, wherein the comparison of the methylation value to the threshold value is predictive of the presence or absence of thyroid cancer in the individual.

11. A computer program product for determining the presence or absence of thyroid cancer in an individual, the computer readable product comprising:

a computer readable medium encoded with program code, the program code including;

program code for receiving a methylation value representing the methylation status of at least one cytosine within a DNA region in a sample from the individual where the DNA region is at least 90% identical to a sequence selected from the group consisting of SEQ ID NO;

436, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, and 485; and

program code for comparing the methylation value to a threshold value, wherein the threshold value distinguishes between individuals with and without thyroid cancer, wherein the comparison of the methylation value to the threshold value is predictive of the presence or absence of thyroid cancer in the individual.