Detecting ovarian cancer

1. A method, comprising:

treating genomic DNA from a biological sample from a human individual having or suspected of having an ovarian cancer with a reagent that modifies DNA in a methylation-specific manner;

amplifying the treated genomic DNA using a set of primers for at least one of CAPN2 and/or SIM2; and

determining a methylation level of at least one differentially methylated region (DMR) in CAPN2 and/or SIM2 using polymerase chain reaction, nucleic acid sequencing, mass spectrometry, methylation-specific nuclease, mass-based separation, or target capture.

2. The method of claim 1 , wherein the biological sample comprises one or more of a plasma sample, a whole blood sample, a leukocyte sample, a serum sample, and an ovarian tissue sample.

3. The method of claim 1 ,

wherein CAPN2 is selected from CAPN2_A and CAPN2_B; and

wherein SIM2 is selected from SIM2_A and SIM2_B.

4. The method of claim 3 , wherein the set of primers for CAPN2_A are capable of binding an amplicon bound by a sequence comprising SEQ ID NO: 53 and SEQ ID NO: 54; and/or wherein the set of primers for CAPN2_B are capable of binding an amplicon bound by a sequence comprising SEQ ID NO: 209 and SEQ ID NO: 210.

5. The method of claim 3 , wherein the set of primers for SIM2_A are capable of binding an amplicon bound by a sequence comprising SEQ ID NO: 29 and SEQ ID NO: 30; and/or wherein the set of primers for SIM2_B are capable of binding an amplicon bound by a sequence comprising SEQ ID NO: 219 and SEQ ID NO: 220.

6. The method of claim 1 , further comprising measuring a level of cancer antigen 125 (CA-125) in the biological sample.

7. The method of claim 1 , wherein the genomic DNA is treated with a bisulfite reagent to produce bisulfite-treated genomic DNA.

8. The method of claim 1 , wherein determining the methylation level of the at least one DMR in CAPN2 and/or SIM2 comprises using one or more methods selected from the group consisting of methylation-specific PCR, quantitative methylation-specific PCR, methylation-specific DNA restriction enzyme analysis, quantitative bisulfite pyrosequencing, flap endonuclease assay, PCR-flap assay, and bisulfite genomic sequencing PCR.

9. The method of claim 1 , wherein amplifying the treated genomic DNA comprises:

using primers specific for a CpG site in CAPN2, wherein the primers specifically bind at least a portion of a genetic region comprising chromosome 1 coordinates 223936858-223937009 or chromosome 1 coordinates 223936868-223937004; and/or

using primers specific for a CpG site in SIM2, wherein the primers specifically bind at least a portion of a genetic region comprising chromosome 21 coordinates 38076882-38077036 or chromosome 21 coordinates 38076892-38077026.

10. The method of claim 1 , wherein the method comprises using a set of primers for CAPN2 and a set of primers for SIM2, and determining a methylation level of at least one DMR in CAPN2 and SIM2.

11. The method of claim 1 , wherein the method further comprises using a set of primers for FAIM2, and determining a methylation level of at least one DMR in FAIM2.

12. The method of claim 11 , wherein FAIM2 is selected from FAIM2_A and FAIM2_B.

13. The method of claim 12 , wherein the set of primers for FAIM2_A are capable of binding an amplicon bound by a sequence comprising SEQ ID NO: 35 and SEQ ID NO: 36; and/or wherein the set of primers for FAIM2_B are capable of binding an amplicon bound by a sequence comprising SEQ ID NO: 189 and SEQ ID NO: 190.

14. The method of claim 11 , wherein amplifying the treated genomic DNA comprises using primers specific for a CpG site in FAIM2, wherein the primers specifically bind at least a portion of a genetic region comprising chromosome 12 coordinates 50297610-50297988 or chromosome 12 coordinates 50297643-50297814.

15. The method of claim 1 , wherein the ovarian cancer is at least one of clear cell ovarian cancer, endometrioid ovarian cancer, mucinous ovarian cancer, and/or serous ovarian cancer.

16. The method of claim 1 , wherein the at least one DMR is present in a coding region or a regulatory region of CAPN2 and/or SIM2.

17. The method of claim 11 , wherein the at least one DMR is present in a coding region or a regulatory region of FAIM2.