1. An assay for detecting the presence of an isocitrate dehydrogenase mutation in a sample obtained from a subject which comprises
determining the methylation status of all or part of the retinol-binding protein 1 (RBP1) promoter in the sample, wherein the presence of the isocitrate dehydrogenase mutation is indicated where the methylation status is hypermethylated.
2. The assay according to claim 1, which comprises characterizing the methylation status to be hypermethylated where the all or part of the RBP1 promoter is significantly more methylated than that of the corresponding part of a standard which is a methylation profile of a wild type RBP1 promoter or a consensus methylation profile of the RBP1 promoters obtained from a plurality of normal subjects.
3. The method according to claim 2, wherein the methylation status is characterized as being hypermethylated where the overall methylation of the all or part of the RBP1 promoter is methylated by 50% or more than that of the corresponding part of the standard.
4. The assay according to claim 1, wherein the RBP1 promoter is located on chromosome 3 at 140740839-140741418.
5. The assay according to claim 1, wherein the part of the RBP1 promoter comprises, consists essentially of, or consists of one or more of the CpG sites of the RBP1 promoter.
6. The assay according to claim 1, wherein the part of the RBP1 promoter comprises, consists essentially of, or consists of CpG sites 5-25 of the CpG island located on chromosome 3 at 140740839-140741418.
7. The assay according to claim 1, wherein the part of the RBP1 promoter comprises, consists essentially of, or consists of at least 3, preferably at least 5, more preferably at least 10 CpG sites selected from the group consisting of CpG sites 14-24, 26-31, 39-45 and 59 of the CpG island located on chromosome 3 at 140740839-140741418.
8. The assay according to claim 1, wherein the part of the RBP1 promoter comprises, consists essentially of or consists of at least 6, preferably at least 10, more preferably at least 15 CpG sites selected from the group consisting of CpG sites 1-5, 14-24, 26-31, 39-45 and 59 of the CpG island located on chromosome 3 at 140740839-140741418.
9. The assay according to claim 1, wherein the part of the RBP1 promoter comprises, consists essentially of, or consists of at least 10, preferably at least 15, more preferably at least 20 CpG sites selected from the group consisting of CpG sites 1-5, 14-24, 26-31, 39-45 and 59-62 of the CpG island located on chromosome 3 at 140740839-140741418.
10. The assay according to claim 4, which comprises characterizing the methylation status as being hypermethylated where the overall methylation of the all or part of the RBP1 promoter is methylated by 50% or more than that of the corresponding part of a standard which is a methylation profile of a wild type RBP1 promoter or a consensus methylation profile of the RBP1 promoters obtained from a plurality of normal subjects.
11. The assay according to claim 1, wherein when one or more of the CpG sites 15, 21, 24, 29, 30, 40, 44 or 45 of the CpG island located on chromosome 3 at 140740839-140741418 are methylated, the methylation status is designated as hypermethylated.
12. The assay according to claim 1, which further comprises designating the presence of the isocitrate dehydrogenase mutation where the methylation status is hypermethylated.
13. The assay according to claim 1, wherein the isocitrate dehydrogenase mutation is an isocitrate dehydrogenase 1 (IDH1) mutation or an isocitrate dehydrogenase 2 (IDH2) mutation.
14. The assay according to claim 1, which comprises modifying all or part of the retinol-binding protein 1 (RBP1) promoter in the sample to make the methylated cytosines of CpG dinucleotides distinguishable from the unmethylated cytosines of CpG dinucleotides.
15. The assay according to claim 14, wherein the modification comprises subjecting all or part of the RBP 1 promoter in the sample to (a) a bisulfite that converts the unmethylated cytosines to uracils, (b) a restriction enzyme that selectively cleaves the unmethylated cytosines, (c) a label specific for either the unmethylated cytosines or the methylated cytosines, or (d) a combination thereof.
16. The assay according to claim 1, wherein the methylation status is determined using reduced representation bisulfite sequencing (RRBS).
17. A method of providing a diagnosis andor prognosis to a subject having a cancer, which comprises
giving the diagnosis andor prognosis to the subject based on the presence or absence of an isocitrate dehydrogenase mutation andor the methylation status of all or part of the retinol-binding protein 1 (RBP1) promoter in a sample obtained from the subject,
wherein the diagnosis is that the cancer may likely be treated with one or more retinoids where the isocitrate dehydrogenase mutation is present andor the all or part of the RBP1 promoter is hypermethylated, and
wherein the prognosis is that the subject will have an estimated time of survival that will likely be increased with treatment with one or more retinoids where the isocitrate dehydrogenase mutation is present andor the all or part of the RBP1 promoter is hypermethylated.
18. A method of treating a subject having a cancer having been determined to be associated with an isocitrate dehydrogenase mutation andor associated with hypermethylation of all or part of the retinol-binding protein 1 (RBP1) promoter, which comprises
administering to the subject one or more retinoids.
19. The method according to claim 17, wherein the presence or association with the isocitrate dehydrogenase mutation andor the methylation status of the all or part of the RBP1 promoter is or was determined using an assay.
20-23. (canceled)
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method of providing solutions for trading securities, the method comprising the steps of:
receiving a level-two quote, the level-two quote comprising a symbol and at least one market participant quote, the market participant quote further comprising a quote price, a quote quantity, a quote market participant identification (\u201cMPID\u201d), and a quote side;
creating in computer memory a solution set comprising at least one solution record corresponding to each market participant quote in the level-two quote, the solution record comprising a solution symbol, a solution side, a solution MPID, a solution price, a solution quantity, and a solution latency, the solution latency comprising a latency for the market identified by the solution MPID; and
sending the solution set to at least one client, wherein the solution record further comprises a type code.
2. The method of claim 1 wherein the client comprises an automated system for trading securities, the method further comprising the steps of:
storing the sent solution set in computer memory in the client system;
using at least one of the sent solution records to create orders for securities; and
deleting from computer memory the used solution records.
3. The method of claim 2 wherein the client comprises more than one automated system for trading securities and the automated systems for trading securities are scaled.
4. The method of claim 1 wherein creating a solution set further comprises recording in the solution record the solution side derived from the quote side, the solution MPID derived from the quote MPID, the solution price derived from the quote price, and the solution symbol derived from the symbol in the level-two quote.
5. The method of claim 1 wherein the solution set comprises at least two solution records, the method further comprising sorting the solution records to yield sorted solution records.
6. The method of claim 5 further comprising sorting the solution records according to side.
7. The method of claim 5 further comprising sorting the solution records according to price.
8. The method of claim 5 further comprising sorting the solution records according to latency.
9. The method of claim 5 further comprising sorting the solution records according to price and latency.
10. The method of claim 5 further comprising sorting the solution records according to side, price, and latency.
11. The method of claim 5 further comprising deleting solution latency from the sorted solution records.
12. The method of claim 1 further comprising creating an index for the solution set.
13. The method of claim 1 wherein latency comprises the difference between the time when a broker-dealer receives from a market a response to an order and the time when the order was sent to the market.
14. A system for providing solutions for trading securities, the system comprising:
means for receiving a level-two quote, the level-two quote comprising a symbol and at least one market participant quote, the market participant quote further comprising a quote price, a quote quantity, a quote market participant identification (\u201cMPID\u201d), and a quote side;
means for creating in computer memory a solution set comprising at least one solution record corresponding to each market participant quote in the level-two quote, the solution record comprising a solution symbol, a solution side, a solution MPID, a solution price, a solution quantity, and a solution latency, the solution latency comprising a latency for a market identified by the solution MPID; and
means for sending the solution set to at least one client, wherein the solution record further comprises a type code.
15. The system of claim 14, wherein the client comprises an automated system for trading securities, the system further comprising:
means for storing the sent solution set in computer memory in the client; means for creating, from at least one of the sent solution records, an order for securities, wherein creating an order from the sent solution record further comprises creating a used solution record; and
means for deleting from computer memory the used solution record.
16. The system of claim 14 wherein the client comprises more than one automated system for trading securities and the automated systems for trading securities are scaled.
17. The system of claim 14 wherein means for creating a solution set further comprises means for recording in the solution record the solution side derived from the quote side, the solution MPID derived from the quote MPID, the solution price derived from the quote price, and the solution symbol derived from the symbol in the level-two quote.
18. The system of claim 14, wherein the solution set comprises at least two solution records, the system further comprising means for sorting the solution records to yield sorted solution records.
19. The system of claim 18 further comprising means for sorting the solution records according to side.
20. The system of claim 18 further comprising means for sorting the solution records according to price.
21. The system of claim 18 further comprising means for sorting the solution records according to latency.
22. The system of claim 18 further comprising means for sorting the solution records according to price and latency.
23. The system of claim 18 further comprising means for sorting the solution records according to side, price, and latency.
24. The system of claim 18 further comprising means for deleting solution latency from the sorted solution records.
25. The system of claim 14 further comprising means for creating an index for the solution set.
26. The system of claim 14 wherein solution latency comprises the difference between the time when a broker-dealer receives from a market a response to an order and the time when the order was sent to the market.
27. A system for providing solutions for trading securities, the system comprising:
a processor coupled to at least one source of quotes and coupled to at least one client, the processor programmed to:
receive at least one level-two quote, the level-two quote comprising a symbol and at least one market participant quote, the market participant quote comprising a quote price, a quote quantity, a quote market participant identification (\u201cMPID\u201d), and a quote side;
create a solution set comprising at least one solution record corresponding to each market participant quote, the solution record comprising a solution symbol, a solution side, a solution MPID, a solution price, a solution quantity, and a solution latency, the solution latency comprising a latency for the market identified by the solution MPED; and
send the solution set to a client; and a memory coupled to the processor, the processor programmed to store the solution set in the memory, wherein the solution record further comprises a type code.
28. The system of claim 27 wherein the client comprises an automated system for trading securities, the system further comprising a client processor coupled to client memory, the client processor programmed to:
store the sent solution set in client memory;
create, dependent upon the sent solution records, orders for securities; and
send the orders for securities to markets.
29. The system of claim 27 wherein the client comprises more than one automated system for trading securities and the automated systems for trading securities are scaled.
30. The system of claim 27 wherein the processor is further programmed to record in the solution set the solution side derived from the quote side, the solution MPID derived from the quote MPID, the solution price derived from the quote price, and the solution symbol derived from the symbol in the level-two quote.
31. The system of claim 27, wherein the solution set comprises at least two solution records, the processor being further programmed the solution records to yield a sorted solution set.
32. The system of claim 31 wherein the processor is further programmed to sort the solution records according to side.
33. The system of claim 31 wherein the processor is further programmed to sort the solution records according to price.
34. The system of claim 31 wherein the processor is further programmed to sort the solution records according to latency.
35. The system of claim 31 wherein the processor is further programmed to sort the solution records according to price and latency.
36. The system of claim 31 wherein the processor is further programmed to sort the solution records according to side, price, and latency.
37. The system of claim 31 wherein the processor is further programmed to delete solution latency from the sorted solution records.
38. The system of claim 27 wherein the processor is further programmed to create an index for the solution set.
39. The system of claim 27 wherein latency comprises the difference between the time when a broker-dealer receives from a market a response to an order and the time when the order was sent to the market.