Ovary Tumor Markers and Methods of Use Thereof

• US 20130004955A1
• Filed: 10/26/2010
• Published: 01/03/2013
• Est. Priority Date: 10/26/2009
• Status: Active Application

• Current Assignee: Externautics SpA
• Original Assignee: Externautics SpA
• Inventors: Grifantini, Renata, Pileri, Piero, Campagnoli, Susanna, Grandi, Alberto, Parri, Matteo, Pierleoni, Andrea, Nogarotto, Renzo
• Granted Patent: US 10,288,617 B2
• Time in Patent Office: Days
• US Class Current: 435/6.12
• CPC Class Codes: C07K 16/3069 Reproductive system, e.g. ovaria, uterus, testes, prostate
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: G01N 2500/02 Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
• CPC Class Codes: G01N 33/57449 of ovaries

Abstract

Newly identified proteins as markers for the detection of ovary tumors, or as therapeutic targets for treatment thereof; affinity ligands capable of selectively interacting with the newly identified markers, methods for tumor diagnosis and therapy using the same.

Claims

1. A tumor marker, for use in the detection of ovary cancer, which is selected from the group consisting of:

i) KLRG2, SEQ ID NO;

85, SEQ ID NO;

86 or a different isoform having sequence identity of at least 80%, preferably at least 90%, more preferably at least 95% to SEQ ID NO;

85, SEQ ID NO;

86 or a nucleic acid molecule containing a sequence coding for a KLRG2 protein, said encoding sequence being preferably selected from SEQ ID NO;

87 and SEQ ID NO;

88;

ii) SLC39A10 in one of its variant isoforms SEQ ID NO;

1, SEQ ID NO;

2 or a different isoform having sequence identity of at least 80%, preferably at least 90%, more preferably at least 95% to SEQ ID NO;

1 or SEQ ID NO;

2;

or a nucleic acid molecule containing a sequence coding for a SLC39A10 protein, said encoding sequence being preferably selected from SEQ ID NO;

3 and SEQ ID NO;

4;

iii) GPR107, in one of its variant isoforms SEQ ID NO;

5, SEQ ID NO;

6, SEQ ID NO;

7, or a different isoform having sequence identity of at least 80%, preferably at least 90%, more preferably at least 95% to any of SEQ ID NO;

5, SEQ ID NO;

6, SEQ ID NO;

7, or a nucleic acid molecule containing a sequence coding for a GPR107 protein, said encoding sequence being preferably selected from SEQ ID NO;

8, SEQ ID NO;

9 and SEQ ID NO;

10;

iv) DPY19L3, in one of its variant isoforms SEQ ID NO;

11, SEQ ID NO;

12, SEQ ID NO;

13, SEQ ID NO;

14, or a different isoform having sequence identity of at least 80%, preferably at least 90%, more preferably at least 95% to SEQ ID NO;

11, SEQ ID NO;

12, SEQ ID NO;

13 or SEQ ID NO;

14, or a nucleic acid molecule containing a sequence coding for a DPY19L3 protein, said encoding sequence being preferably selected from SEQ ID NO;

15, SEQ ID NO;

16, SEQ ID NO;

17 and SEQ ID NO;

18;

v) FLJ42986, SEQ ID NO;

19 or a different isoform having sequence identity of at least 80%, preferably at least 90%, more preferably at least 95% to SEQ ID NO;

19, or a nucleic acid molecule containing a sequence coding for a FLJ42986 protein, said encoding sequence being preferably SEQ ID NO;

20;

vi) COL20A1, in one of its variant isoforms SEQ ID NO;

21, SEQ ID NO;

22, SEQ ID NO;

23, or a different isoform having sequence identity of at least 80%, preferably at least 90%, more preferably at least 95% to any of SEQ ID NO;

21, SEQ ID NO;

22, SEQ ID NO;

23, or a nucleic acid molecule containing a sequence coding for a COL20A1 protein, said encoding sequence being preferably selected from SEQ ID NO;

24, SEQ ID NO;

25 and SEQ ID NO;

26;

vii) GLT25D2, in one of its variant isoforms SEQ ID NO;

27, SEQ ID NO;

28, SEQ ID NO;

29, SEQ ID NO;

30, or a different isoform having sequence identity of at least 80%, preferably at least 90%, more preferably at least 95% to any of SEQ ID NO;

27, SEQ ID NO;

28, SEQ ID NO;

29, SEQ ID NO;

30, or a nucleic acid molecule containing a sequence coding for a GLT25D2 protein, said encoding sequence being preferably selected from SEQ ID NO;

31, SEQ ID NO;

32, SEQ ID NO;

33 and SEQ ID NO;

34;

viii) SYTL3, in one of its variant isoforms SEQ ID NO;

35, SEQ ID NO;

36, SEQ ID NO;

37, or a different isoform having sequence identity of at least 80%, preferably at least 90%, more preferably at least 95% to any of SEQ ID NO;

35, SEQ ID NO;

36, SEQ ID NO;

37, or a nucleic acid molecule containing a sequence coding for a SYTL3 protein, said encoding sequence being preferably selected from SEQ ID NO;

38, SEQ ID NO;

39 and SEQ ID NO;

40;

ix) DENND1B;

in one of its variant isoforms SEQ ID NO;

41, SEQ ID NO;

42, SEQ ID NO;

43, SEQ ID NO;

44, or a different isoform having sequence identity of at least 80%, preferably at least 90%, more preferably at least 95% to any of SEQ ID NO;

41, SEQ ID NO;

42, SEQ ID NO;

43, SEQ ID NO;

44, or a nucleic acid molecule containing a sequence coding for a DENND1B protein, said encoding sequence being preferably selected from SEQ ID NO;

45, SEQ ID NO;

46, SEQ ID NO;

47 and SEQ ID NO;

48;

x) FLJ3710, SEQ ID NO;

49 or a different isoform having sequence identity of at least 80%, preferably at least 90%, more preferably at least 95% to SEQ ID NO;

49, or a nucleic acid molecule containing a sequence coding for a FLJ3710 protein, said encoding sequence being preferably SEQ ID NO;

50;

xi) Chromosome 6 orf 98 (C6orf98) SEQ ID NO;

51 or a different isoform having sequence identity of at least 80%, preferably at least 90%, more preferably at least 95% to SEQ ID NO;

51, or a nucleic acid molecule containing a sequence coding for a C6orf98 protein, said encoding sequence being preferably SEQ ID NO;

52;

xii) Family with sequence similarity 69, member B (Fam69B) SEQ ID NO;

53, SEQ ID NO;

54 or a different isoform having sequence identity of at least 80%, preferably at least 90%, more preferably at least 95% to SEQ ID NO;

53 or SEQ ID NO;

54, or a nucleic acid molecule containing a sequence coding for a Fam69B protein, said encoding sequence being preferably selected from SEQ ID NO;

55 and SEQ ID NO;

56;

xiii) EMI domain-containing protein 1 Precursor (EMID1) in one of its variant isoforms SEQ ID NO;

57, SEQ ID NO;

58, SEQ ID NO;

59, SEQ ID NO;

60, SEQ ID NO;

61, SEQ ID NO;

62, SEQ ID NO;

63, SEQ ID NO;

64, SEQ ID NO;

65, SEQ ID NO;

66, SEQ ID NO;

67, SEQ ID NO;

68, SEQ ID NO;

69, SEQ ID NO;

70, or a different isoform having sequence identity of at least 80%, preferably at least 90%, more preferably at least 95% to SEQ ID NO;

57, SEQ ID NO;

58, SEQ ID NO;

59, SEQ ID NO;

60, SEQ ID NO;

61, SEQ ID NO;

62, SEQ ID NO;

63, SEQ ID NO;

64, SEQ ID NO;

65, SEQ ID NO;

66, SEQ ID NO;

67, SEQ ID NO;

68, SEQ ID NO;

69, SEQ ID NO;

70, or a nucleic acid molecule containing a sequence coding for a Fam69B protein, said encoding sequence being preferably selected from SEQ ID NO;

71, SEQ ID NO;

72, SEQ ID NO;

73, SEQ ID NO;

74, SEQ ID NO;

75, SEQ ID NO;

76, SEQ ID NO;

77, SEQ ID NO;

78, SEQ ID NO;

79, SEQ ID NO;

80, SEQ ID NO;

81, SEQ ID NO;

82, SEQ ID NO;

83 and SEQ ID NO;

84;

xiv) ERMP1, SEQ ID NO;

89, SEQ ID NO;

90 SEQ ID NO;

91, or a different isoform having sequence identity of at least 80%, preferably at least 90%, more preferably at least 95% to SEQ ID NO;

89, SEQ ID NO;

90 or SEQ ID NO;

91, or a nucleic acid molecule containing a sequence coding for a ERMP1 protein, said encoding sequence being preferably selected from SEQ ID NO;

92, SEQ ID NO;

93 and SEQ ID NO;

94;

xv) VMO1, SEQ ID NO;

95, SEQ ID NO;

96, SEQ ID NO;

97, SEQ ID NO;

98 or a different isoform having sequence identity of at least 80%, preferably at least 90%, more preferably at least 95% to SEQ ID NO;

95, SEQ ID NO;

96, SEQ ID NO;

97, SEQ ID NO;

98 or a nucleic acid molecule containing a sequence coding for a VMO1 protein, said encoding sequence being preferably selected from SEQ ID NO;

99, SEQ ID NO;

100;

SEQ ID NO;

101 and SEQ ID NO;

102.

2. A method of screening an ovary tissue sample for malignancy, said method comprising determining the presence in said sample of at least one of the tumor markers of claim 1 or a combination thereof.

3. A method according to claim 2, wherein the tumor marker is a protein, said method being based on immunoradiometric, immunoenzymatic or immunohistochemical techniques.

4. A method according to claim 2, wherein the tumor marker is a nucleic acid molecule, said method being based on polymerase chain reaction techniques.

5. A method in vitro for determining the presence of an ovary tumor in a subject, which comprises the steps of:

(a) providing a sample of the tissue suspected of containing tumor cells;

(b) determining the presence of a tumor marker according to claim 1 or a combination thereof in said tissue sample by detecting the expression of the marker protein or the presence of the respective mRNA transcript;

wherein the detection of one or more tumor markers in the tissue sample is indicative of the presence of ovary tumor in said subject.

6. A method of screening a test compound as an antitumor candidate, which comprises contacting cells expressing a tumor marker protein according to claim 1 with the test compound, and determining the binding of said compound to said tumor marker.

7. An antibody or a fragment thereof which is able to specifically recognize and bind to one of the tumor marker proteins according to claim 1.

8. An antibody according to claim 7, which is either monoclonal or polyclonal.

9. (canceled)

10. (canceled)

11. A siRNA molecule having a sequence complementary to one of SEQ ID NOs:

103 through SEQ ID NO;

108, for use in tumor-gene silencing.