METHOD OF DIAGNOSING NEOPLASMS

• US 20100292094A1
• Filed: 10/23/2008
• Published: 11/18/2010
• Est. Priority Date: 10/23/2007
• Status: Abandoned Application

• Current Assignee: Clinical Genomics Pty Ltd., Commonwealth Scientific & Industrial Research Organisation (Commonwealth Of Australia As Represented By Department Of Industry, Innovation, Climate Change, Science, Research And Tertiary Education)
• Original Assignee: Clinical Genomics Pty Ltd., Commonwealth Scientific & Industrial Research Organisation (Commonwealth Of Australia As Represented By Department Of Industry, Innovation, Climate Change, Science, Research And Tertiary Education)
• Inventors: Wilson, William J., Dunne, Robert, Lockett, Trevor John, Lapointe, Lawrence Charles, Young, Graeme P.
• Application Number:
  US12/739,580
• Publication Number:
  US 20100292094A1
• Time in Patent Office: Days
• US Class Current: 506/9
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: C12Q 2600/16 Primer sets for multiplex assays
• CPC Class Codes: G01N 2800/06 Gastro-intestinal diseases
• CPC Class Codes: G01N 33/57446 of stomach or intestine

Abstract

The present invention relates generally to nucleic acid molecules, the RNA and protein expression profiles of which are indicative of the onset, predisposition to the onset and/or progression of a neoplasm. More particularly, the present invention is directed to nucleic acid molecules, the expression profiles of which are indicative of the onset and/or progression of a large intestine neoplasm, such as an adenoma or an adenocarcinoma. The expression profiles of the present invention are useful in a range of applications including, but not limited to, those relating to the diagnosis and/or monitoring of colorectal neoplasms, such as colorectal adenocarcinomas. Accordingly, in a related aspect the present invention is directed to a method of screening a subject for the onset, predisposition to the onset and/or progression of a neoplasm by screening for modulation in the expression profile of one or more nucleic acid molecule markers.

Claims

1-30. -30. (canceled)

31. A method of screening for the onset or predisposition to the onset of a large intestine neoplasm or monitoring the progress of a neoplasm in an individual, said method comprising measuring the level of expression of one or more genes or transcripts selected from:

32. The method according to claim 31 wherein said one or more genes or transcripts are selected from:

(i) 201563_at, 204702_s_at; and

/or

(ii) SORD, NFE2L3.

33. The method according to claim 31 wherein said one or more genes or transcripts are selected from:

(i) the gene, genes or transcripts detected by Affymetrix probeset IDs;

225681_at;

227140_at; and

/or

(ii) CTHRC1;

(ii) the gene, genes or transcripts detected by Affymetrix probeset IDs;

227475_at, 204475_at, 202859_x_at, 202404_s_at; and

/or

FOXQ1, MMP1, IL8, COL1A2;

(iii) the gene, genes or transcripts detected by Affymetrix probeset IDs;

205513_at, 204259_at, 227174_at, 210511_s_at, 37892_at; and

/or

TCN1, MMP7, WDR72, INHBA, COL11A1;

34. The method according to any one of claims 31-33 wherein said control level is a non-neoplastic level.

35. The method according to claim 31 wherein said neoplastic cell is an adenoma or an adenocarcinoma.

36. The method according to claim 31 wherein said neoplasm is an adenoma and said one or more genes or transcripts are selected from:

37. The method according to claim 31 wherein said neoplasm is a cancer and said one or more genes or transcripts are selected from:

47. The method according to any one of claim 31, 38, 43 or 44 wherein said cell is a colorectal cell.

48. The method according to any one of claim 31, 38, 43 or 44 wherein said biological sample is a faecal sample, enema wash, surgical resection, tissue biopsy or blood sample.

49. The method according to any one of claim 31, 38, 43 or 44 wherein said level of expression is mRNA expression or protein expression.

50. The method according to any one of claim 31, 38, 43 or 44 wherein said individual is a human.

51. A molecular array, which array comprises a plurality of:

nucleic acid molecules comprising a nucleotide sequence corresponding to any one or more of the neoplastic marker genes listed in claim 31 or a sequence exhibiting at least 80% identity thereto or a functional derivative, fragment, variant or homologue of said nucleic acid molecule;

or

(ii) nucleic acid molecules comprising a nucleotide sequence capable of hybridising to any one or more of the sequences of (i) under medium stringency conditions or a functional derivative, fragment, variant or homologue of said nucleic acid molecule;

or

(iii) nucleic acid probes or oligonucleotides comprising a nucleotide sequence capable of hybridising to any one or more of the sequences of (i) under medium stringency conditions or a functional derivative, fragment, variant or homologue of said nucleic acid molecule;

or

(iv) probes capable of binding to any one or more of the proteins encoded by the nucleic acid molecules of (i) or a derivative, fragment or, homologue thereof

wherein the level of expression of said marker genes of (i) or proteins of (iv) is indicative of the neoplastic state of a cell or cellular subpopulation derived from the large intestine.

52. The method according to any one of claim 31, 38, 43 or 44 wherein said control level is a non-neoplastic level.

38. A method of screening for the onset of a large intestine neoplasm in an individual, said method comprising measuring the level of expression of one or more genes or transcripts selected from:

39. The method according to claim 38 wherein said neoplastic cell is an adenoma or adenocarcinoma.

40. The method according to claim 38 wherein said neoplasm is an adenoma and said one or more genes or transcripts are selected from:

(i) the gene, genes or transcripts detected by Affymetrix probeset IDs;

204885_s_at, 217523_at, 236894_at, 205174_s_at, 228915_at, 238984_at, 205825_at, 235976_at, 241031_at; and

/or

(ii) CD44, MSLN, QPCT, DACH1, NLF1, REG4, L1TD1, PCSK1, SLITRK6.

41. The method according to claim 38 wherein said neoplasm is a cancer and said one or more genes or transcripts are selected from:

42. The method according to any one of claims 38-41 wherein said background level is the background of the testing methodology.

43. A method of characterising a neoplastic cell or cellular population, which cell or cellular population is derived from the large intestine of an individual, said method comprising measuring the level of expression of one or more genes or transcripts selected from:

45. The method according to claim 43 wherein said one or more genes or transcripts are selected from:

(i) the gene or genes detected by Affymetrix probeset IDs;

210107_at; and

/or

CLCA1;

(ii) the gene, genes or transcripts detected by Affymetrix probeset IDs;

203240_at, 219955_at, 242601_at, 204607_at, 232481_s_at, 227725_at, 223969_s_at, 228232_s_at; and

/or

FCGBP, LITD1, LOC253012, HMGCS2, SLITRK6, ST6GALNAC1, RETNLB, VSIG2;

(iii) said control level is the background level of neoplastic tissue and said one or more genes or transcripts are selected from;

44. A method of characterising a neoplastic cell or cellular population, which cell or cellular population is derived from the large intestine of an individual, said method comprising measuring the level of expression of one or more genes or transcripts selected from:

46. The method according to claim 44 wherein said one or more genes or transcripts are selected from:

(i) the gene, genes or transcripts detected by Affymetrix probeset IDs;

202404_s_at, 210809_s_at, 227140_at, 225681_at, 209875_s_at, 204475_at, 212464_s_at; and

/or

COL1A2, FN1, SPP1, CTHRC1, POSTN, MMP1;

(ii) the gene, genes or transcripts detected by Affymetrix probeset IDs;

200665_s_at, 218468_s_at, 211959_at, 201744_s_at, 202859_x_at; and

/or

SPARC, GREM1, IGFBP5, LUM, IL8;