Method for determining rcc subtypes

Patent metadata

Field	Value
Publication number	US-2022098677-A1
Application number	US-202117496641-A
Country	US
Kind code	A1
Filing date	Oct 7, 2021
Priority date	Apr 12, 2019
Publication date	Mar 31, 2022
Grant date	—

Abstract

The present invention relates to a method for determining in a subject's biological sample the relative proportions of papillary renal cell carcinoma (pRCC), clear cell renal cell carcinoma (ccRCC), and chromophobe renal cell carcinoma (chRCC), an array comprising capture molecules capable of specifically binding to RCC signature genes or coding sequences thereof or products encoded thereby, and the use of RCC signature genes for classifying a subject into a renal cell carcinoma (RCC) risk group and/or for determining in a subject's biological sample the relative proportions of pRCC, ccRCC, and chRCC.

First claim

Therefore, what is claimed, is:

1 . A method for determining in a subject's biological sample the relative proportions of papillary renal cell carcinoma (pRCC), clear cell renal cell carcinoma (ccRCC), and chromophobe renal cell carcinoma (chRCC), the method comprising:
(a) Providing a biological sample from a subject suspected of being affected by RCC, (b) Assaying said biological sample to determine expression level values of
at least one of the signature genes listed in Table 1,
at least one of the signature genes listed in Table 2, and
at least one of the signature genes listed in Table 3,
(c) Subjecting the obtained expression level values to a signal separation method, thereby determining relative proportions of pRCC, ccRCC, and chRCC in said biological sample.

2 . The method of claim 1 , wherein in step (b) said biological sample is assayed to determine expression level values of
at least two of the signature genes listed in Table 1, at least two of the signature genes listed in Table 2, and at least two of the signature genes listed in Table 3.

3 . The method of claim 1 , wherein the signal separation method is a method selected from the group consisting of: blind signal separation method, deconvolution, and computational deconvolution.

4 . The method of claim 1 , wherein after step (c) the following step is carried out:
(d) Classifying the subject into a risk group on the basis of the relative proportions of at least one of pRCC, ccRCC, and chRCC in said biological sample.

5 . The method of claim 1 , wherein after step (c) the following step is carried out:
(d) Classifying the subject into a risk group on the basis of the relative proportions of hccRCC in said biological sample.

6 . The method of claim 4 , wherein the risk group is selected from “low risk”, “intermediate risk”, and “high risk” according to the prognosis for the subject.

7 . The method of claim 6 , wherein the “low risk” group is determined by a relative ccRCC proportion in a range which is selected from the group consisting of: about ≥0 to ≤12%, about ≥0 to ≤5%, about ≥0 to 3%, and about 0%.

8 . The method of claim 6 , wherein the “intermediate risk” group is determined by a relative ccRCC proportion in a range which is selected from the group consisting of: about ≥7.5 to ≤25%, about ≥10 to ≤20%, and about ≥13 to ≤17%.

9 . The method of claim 6 , wherein the “intermediate risk” group is determined by a relative ccRCC proportion in a range which is selected from the group consisting of: about ≥62.5%, about ≥70%, %, about ≥77.5%, about ≥90%, and about 100%.

10 . The method of claim 7 , wherein the “high risk” group is determined by a relative ccRCC proportion in a range which is selected from the group consisting of: about ≥16 to ≤77.5%, about ≥20 to ≤70%, about ≥55 to ≤62.5%, and about 40%.

11 . The method of claim 1 , wherein in step (b) the assaying involves the use of RNA sequencing, PCR-based method, microarray-based method, hybridization-based method, and antibody-based method.

12 . An array comprising capture molecules capable of specifically binding to
biomolecules encoding or encoded by at least one of the signature genes listed in Table 1 or segments thereof, biomolecules encoding or encoded by at least one of the signature genes listed in Table 2 or segments thereof, and biomolecules encoding or encoded by at least one of the signature genes listed in Table 3.

13 . An array comprising capture molecules capable of specifically binding to
biomolecules encoding or encoded by at least two of the signature genes listed in Table 1 or segments thereof, biomolecules encoding or encoded by at least two of the signature genes listed in Table 2 or segments thereof, and biomolecules encoding or encoded by at least two of the signature genes listed in Table 3.

14 . The array of claim 12 , wherein said biomolecules are selected from the group consisting of: nucleic acid molecules, proteins, and peptides.

15 . The array of claim 13 , wherein said biomolecules are selected from the group consisting of: nucleic acid molecules, proteins, and peptides.

16 . The array of claim 12 , wherein said capture molecules are selected from the group consisting of: nucleic acid molecules, antibodies and fragments thereof.

17 . The array of claim 13 , wherein said capture molecules are selected from the group consisting of: nucleic acid molecules, antibodies and fragments thereof.

Assignees

• Robert Bosch Ges Fuer Medizinische Forschung Mbh
• Univ Tuebingen Medizinische Fakultaet
• Univ Friedrich Alexander Er

Inventors

• Buettner Florian
• Schaeffeler Elke
• Schwab Matthias
• Winter Stefan
• Bedke Jens
• Stenzl Arnulf
• Hartmann Arndt

Classifications

• C12Q2600/118

  Prognosis of disease development · CPC title

• C12Q1/6886 Primary

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

• C12Q2600/158

  Expression markers · CPC title

• C12Q2600/112

  Disease subtyping, staging or classification · CPC title