# US 2024/0200149 A1 · Method for analyzing probability of suffering from cancer in subject

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- Number: US 2024/0200149 A1
- Document ID: US20240200149A1
- Status: Published application
- Kind: A1
- Application number: 18/591,077
- Filed: 2024-02-29
- Published: 2024-06-20
- Earliest claimed: 2022-09-20
- Assignees: Kabushiki Kaisha Toshiba
- Applicants: Kabushiki Kaisha Toshiba
- Inventors: Tomomi ANDO; Mitsuko ISHIHARA; Yoshitake SANO; Takuya MIYAGAWA; Koji HASHIMOTO
- Web page: https://patentgrep.com/patent/US20240200149A1

## CPC

- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- C12Q 1/68: involving nucleic acids
- C12Q 1/686: Polymerase chain reaction [PCR]
- C12Q 1/6869: Methods for sequencing
- C12Q 1/6874: involving nucleic acid arrays, e.g. sequencing by hybridisation
- G01N 33/53: Immunoassay; Biospecific binding assay; Materials therefor
- C12Q 2600/16: Primer sets for multiplex assays
- C12Q 2600/178: miRNA, siRNA or ncRNA
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

According to one embodiment, a method for analyzing the probability of suffering from cancer in a subject is provided. The method includes counting the number of types of RNA in a sample derived from the subject with respect to the types of RNAs in which sequence variation based on RNA editing exists in comparison with a reference sequence, and determining the probability of suffering from cancer in the subject by using the number of types of RNAs obtained as an index.

## Claims

### Claim 1

A method for analyzing the probability of suffering from cancer in a subject, comprising:
counting the number of types of RNA in a sample derived from the subject with respect to the types of RNAs in which sequence variation based on RNA editing exists in comparison with a reference sequence; and
determining the probability of suffering from cancer in the subject by using the number of types of RNAs obtained as an index.

### Claim 2 (depends on 1)

The analytic method of claim 1, wherein the sample derived from the subject is a body fluid, and the counting and the determining comprise:
acquiring sample data by acquiring information on sequence variation from a reference sequence from the body fluid;
extracting features by counting the number of types of RNAs in which the sequence variation exists; and
determining morbidity of cancer by using the number of types of RNAs having sequence variation as an index to identify a possibility of suffering from cancer.

### Claim 3 (depends on 1)

The analytic method of claim 1, further comprising comparing the number of types of the RNA from the subject and the number of types of the RNA obtained from a sample derived from a non-cancerous individual with each other.

### Claim 4 (depends on 3)

The method of claim 3, wherein when the number of the types of RNAs from the subject is greater than the number of the types of RNAs from the non-cancerous individual, the subject is identified as likely to have cancer, and when the number of the types of RNAs from the subject is less than or equal to the number of the types of RNAs from the non-cancer individual, the subject is identified as unlikely to have cancer.

### Claim 5 (depends on 2)

The method of claim 2, wherein
the body fluid is blood, serum or plasma.

### Claim 6 (depends on 1)

The method of claim 1, wherein the RNA is miRNA, mRNA, tRNA, or piRNA.

### Claim 7 (depends on 3)

The method of claim 3, wherein the RNA is miRNA, mRNA, tRNA, or piRNA.

### Claim 8 (depends on 4)

The method of claim 4, wherein
the RNA is miRNA, mRNA, tRNA, or piRNA.

### Claim 9 (depends on 1)

The method of claim 1, wherein
the sequence variation is caused by an RNA editing enzyme.

### Claim 10 (depends on 1)

The method of claim 1, wherein
the sequence variation is a base substitution.

### Claim 11

A method for analyzing probability of suffering from cancer in a subject, comprising:
classifying RNAs contained in a sample derived from a subject according to homology of a sequence thereof to a reference sequence;
determining a group of representative sequences having identical sequences in an RNA population classified for each of the reference sequence;
comparing each sequence in the representative sequence group with the corresponding reference sequence to detect sequence variation in each; and
counting the number of types of the representative sequences having the sequence variation.

### Claim 12 (depends on 1)

The method of claim 1, wherein the RNA is miRNA and the cancer is at least one type of cancer selected from the group consisting of breast cancer, colorectal cancer, lung cancer, stomach cancer, pancreatic cancer, cervical cancer, uterine cancer, ovarian cancer, sarcoma, prostate cancer, bile duct cancer, bladder cancer, esophagus cancer, liver cancer, brain tumor, and kidney cancer.

### Claim 13 (depends on 1)

The method for analyzing the probability of suffering from cancer in a subject, of claim 1, further comprising:
classifying RNAs contained in each of samples derived from a subject or a cancer individual and from a non-cancer individual, by homology of the RNA with respect to a reference sequence;
determining a representative sequence group having identical sequences in the RNA population classified for the reference sequence;
comparing each sequence of the representative sequence group to each corresponding reference sequence for samples derived from the subject or cancer individual and samples derived from controls, and detecting the sequence variation;
counting the number of types of representative sequences having the sequence variation; and
comparing the number of types of representative sequences counted in the subject or cancer individual and the number of types of representative sequences counted in the controls, and determining a threshold for discriminating the subjects or cancer individuals from the controls.

### Claim 14 (depends on 1)

The method for analyzing the probability of suffering from cancer in the subject of claim 1, wherein
the determining as the index is performed by: classifying RNAs contained in each of samples derived from a subject or a cancer individual and from a non-cancer individual, by homology of the RNA with respect to a reference sequence;
determining a representative sequence group having identical sequences in the RNA population classified for the reference sequence;
comparing each sequence of the representative sequence group to each corresponding reference sequence for samples derived from the subject or cancer individual and samples derived from controls, and detecting the sequence variation;
counting the number of types of representative sequences having the sequence variation; and
comparing the number of types of representative sequences counted in the subject or cancer individual and the number of types of representative sequences counted in the controls, and determining a threshold for discriminating the subjects or cancer individuals from the controls, and
the threshold value is greater than the number obtained for the sequence variation in the group of cancer individuals than the number obtained from the group of non-cancer individuals.

### Claim 15 (depends on 14)

The method for analyzing the probability of suffering from cancer in the subject of claim 14, wherein
the threshold value is an integer greater than or equal to 2.

### Claim 16 (depends on 14)

The method for analyzing the probability of suffering from cancer in the subject of claim 14, wherein
the threshold value is determined by a method and the type of RNA used therein.

### Claim 17 (depends on 14)

The method for analyzing the probability of suffering from cancer in the subject of claim 14,
wherein at least one method from the group consisting of NGS, qPCR, Sanger sequencing, microarray, and hybridization is selected and used.

### Claim 18

A method for detecting sequence variation, comprising:
classifying RNAs contained in a sample derived from a subject by homology of the sequence thereof to a reference sequence;
determining a group of representative sequences having identical sequences in an RNA population classified for each of the reference sequence;
comparing each sequence of the representative sequence group with the corresponding reference sequence, and detecting sequence variations; and
counting the number of types of the sequence variations.

### Claim 19 (depends on 18)

The method for detecting sequence variation, of claim 18, wherein
in a specific sequence of the representative sequence group, occurrence of sequence variation in comparison with a corresponding reference sequence, can be identified together with sequence information of the specific representative sequence.

### Claim 20 (depends on 19)

The method for detecting sequence variation, of claim 19, wherein
at least one method from the group consisting of NGS, qPCR, Sanger sequencing, microarray, and hybridization is selected and used.
