Compositions and methods for determining endometrial cancer prognosis

Patent metadata

Field	Value
Publication number	US-2018094301-A1
Application number	US-201615548816-A
Country	US
Kind code	A1
Filing date	Feb 5, 2016
Priority date	Feb 6, 2015
Publication date	Apr 5, 2018
Grant date	—

Abstract

The present invention provides methods and compositions for determining prognosis in individual with cancer, in particular endometrial cancer. The present invention also provides methods of developing and using predictive models that are useful for determining prognosis of endometrial cancer and other similar diseases. The present invention further provides methods for determining microsatellite status using next generation sequencing.

First claim

What is claimed is:

1 . A method of determining the risk of recurrence of endometrial cancer in a subject comprising:
a) obtaining a sample from the subject; b) testing the sample for a mutation in the ESR1 gene; and c) indicating the subject is not at risk of recurrence if the ESR1 gene is not mutated or the subject is at risk of recurrence if the ESR1 gene is mutated.

2 . The method of claim 1 , wherein the endometrial cancer is stage I/II.

3 . The method of claim 2 , wherein the stage I/II endometrial cancer further comprises low copy number changes and microsatellite instability.

4 . The method of claim 1 , wherein the mutation in the ESR1 gene is a Y537 substitution.

5 . The method of claim 1 , wherein the mutation in the ESR1 gene is an in-frame deletion.

6 . The method of claim 1 , further comprising administering to the subject a compound for treating endometrial cancer when the ESR1 gene is mutated.

7 . The method of claim 1 , wherein the subject has previously undergone surgery to remove an endometrial tumor.

8 . The method of claim 1 , wherein the subject is non-symptomatic.

9 . The method of claim 1 , wherein the subject is in remission.

10 . A method of predicting recurrence in a subject with endometrial cancer comprising:
a) obtaining a sample from the subject; b) testing the sample for a mutation in the ESR1 gene; and c) indicating the subject will experience cancer recurrence if the ESR1 gene is mutated and the subject will not experience cancer recurrence if the ESR1 gene is not mutated.

11 . The method of claim 10 , wherein the endometrial cancer is stage I/II.

12 . The method of claim 11 , wherein the stage I/II endometrial cancer further comprises low copy number changes and microsatellite instability.

13 . The method of claim 10 , wherein the mutation in the ESR1 gene is a Y537 substitution.

14 . The method of claim 10 , wherein the mutation in the ESR1 gene is an in-frame deletion.

15 . The method of claim 10 , further comprising administering to the subject a compound for treating endometrial cancer when the ESR1 gene is mutated.

16 . The method of claim 10 , wherein the subject has previously undergone surgery to remove an endometrial tumor.

17 . The method of claim 10 , wherein the subject is non-symptomatic.

18 . The method of claim 10 , wherein the subject is in remission.

19 . A method for guiding treatment in a subject with endometrial cancer comprising:
a) obtaining a sample from the subject; b) testing the sample for a mutation in the ESR1 gene; and c) indicating the subject should receive chemotherapy if the ESR1 gene is mutated.

20 . The method of claim 19 , wherein the endometrial cancer is stage I/II.

21 . The method of claim 20 , wherein the stage I/II endometrial cancer further comprises low copy number changes and microsatellite instability.

22 . The method of claim 19 , wherein the mutation in the ESR1 gene is a Y537 substitution.

23 . The method of claim 19 , wherein the mutation in the ESR1 gene is an in-frame deletion.

24 . The method of claim 19 , wherein the subject has previously undergone surgery to remove an endometrial tumor.

25 . The method of claim 19 , wherein the subject is non-symptomatic.

26 . The method of claim 19 , wherein the subject is in remission.

27 . A method of determining the risk of recurrence of endometrial cancer in a subject comprising:
a) obtaining a sample from the subject; b) testing the sample for a mutation in the CSDE1 gene; and c) indicating the subject is not at risk of recurrence if the CSDE1 gene is not mutated or the subject is at risk of recurrence if the CSDE1 gene is mutated.

28 . The method of claim 27 , wherein the endometrial cancer is stage I/II.

29 . The method of claim 28 , wherein the stage I/II endometrial cancer further comprises low copy number changes and microsatellite instability.

30 . The method of claim 27 , further comprising administering to the subject a compound for treating endometrial cancer when the CSDE1 gene is mutated.

31 . The method of claim 27 , wherein the subject has previously undergone surgery to remove an endometrial tumor.

32 . The method of claim 27 , wherein the subject is non-symptomatic.

33 . The method of claim 27 , wherein the subject is in remission.

34 . A method of predicting recurrence in a subject with endometrial cancer comprising:
a) obtaining a sample from the subject; b) testing the sample for a mutation in the CSDE1 gene; and c) indicating the subject will experience cancer recurrence if the CSDE1 gene is mutated and the subject will not experience cancer recurrence if the CSDE1 gene is not mutated.

35 . The method of claim 34 , wherein the endometrial cancer is stage I/II.

36 . The method of claim 35 , wherein the stage I/II endometrial cancer further comprises low copy number changes and microsatellite instability.

37 . The method of claim 34 , further comprising administering to the subject a compound for treating endometrial cancer when the CSDE1 gene is mutated.

38 . The method of claim 34 , wherein the subject has previously undergone surgery to remove an endometrial tumor.

39 . The method of claim 34 , wherein the subject is non-symptomatic.

40 . The method of claim 34 , wherein the subject is in remission.

41 . A method for guiding treatment in a subject with endometrial cancer comprising:
a) obtaining a sample from the subject; b) testing the sample for a mutation in the CSDE1 gene; and c) indicating the subject should receive chemotherapy if the CSDE1 gene is mutated.

42 . The method of claim 41 , wherein the endometrial cancer is stage I/II.

43 . The method of claim 42 , wherein the stage I/II endometrial cancer further comprises low copy number changes and microsatellite instability.

44 . The method of claim 41 , wherein the subject has previously undergone surgery to remove an endometrial tumor.

45 . The method of claim 41 , wherein the subject is non-symptomatic.

46 . The method of claim 41 , wherein the subject is in remission.

47 . A method of determining the risk of recurrence of endometrial cancer in a subject comprising:
a) obtaining a sample from the subject; b) testing the sample for a mutation in the SGK1 gene; and c) indicating the subject is not at risk of recurrence if the SGK1 gene is not mutated or the subject is at risk of recurrence if the SGK1 gene is mutated.

48 . The method of claim 47 , wherein the endometrial cancer is stage I/II.

49 . The method of claim 48 , wherein the stage I/II endometrial cancer further comprises low copy number changes and microsatellite instability.

50 . The method of claim 47 , further comprising administering to the subject a compound for treating endometrial cancer when the SGK1 gene is mutated.

51 . The method of claim 47 , wherein the subject has previously undergone su

Assignees

• Quest Diagnostics Invest Llc

Inventors

• Wang Yongbao
• Arvai Kevin J
• Jones Daniel

Classifications

• C12Q2600/118

  Prognosis of disease development · CPC title

• C12Q1/6811 Primary

  Selection methods for production or design of target specific oligonucleotides or binding molecules · CPC title

• C12Q1/686

  Polymerase chain reaction [PCR] · CPC title

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• C12Q1/6886 Primary

  for cancer (immunoassay for cancer G01N33/575) · CPC title