# US 10,870,890 B2 · TERT promoter mutations in urothelial neoplasia

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- Number: US 10,870,890 B2
- Document ID: US10870890B2
- Status: Granted
- Kind: B2
- Application number: 15/077,284
- Filed: 2016-03-22
- Published: 2016-07-21
- Granted: 2020-12-22
- Earliest claimed: 2013-02-18
- Assignees: The Johns Hopkins University
- Applicants: The Johns Hopkins University
- Inventors: Bert Vogelstein; Kenneth W. Kinzler; Luis Diaz; Nickolas Papadopoulos; George J. Netto; Ralph Hruban; Isaac A. Kinde
- Web page: https://patentgrep.com/patent/US10870890B2

## CPC

- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- C12Q 2600/156: Polymorphic or mutational markers
- 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

## Abstract

TERT promoter mutations occur in both papillary and flat lesion bladder cancers, are the most frequent genetic alterations identified to date in noninvasive precursor lesions of the bladder, are detectable in urine, and appear to be strongly associated with bladder cancer recurrence. The TERT promoter mutations are useful urinary biomarker for both the early detection and monitoring of bladder neoplasia.

## Claims

### Claim 1

A method of detecting a somatic mutation and treating bladder cancer in a human subject comprising:
detecting in a nucleic acid obtained from a urine sample of the human subject the presence of a somatic mutation in a promoter of telomerase reverse transcriptase (TERT) gene, wherein the somatic mutation is present at position 1,295,228 on the minus strand of chromosome 5 of version hg19 of the human genome sequence,
wherein the detecting is performed by amplifying a nucleic acid sequence comprising the TERT promoter, or a portion thereof, to form an amplicon and sequencing the amplicon; and
treating the human subject with the somatic mutation in the TERT gene for bladder cancer by a therapy chosen from a chemotherapy, a biological agent, a surgery, or a radiation therapy.

### Claim 2 (depends on 1)

The method of claim 1, wherein the human subject has a transitional cell carcinoma of the urothelial tract.

### Claim 3 (depends on 1)

The method of claim 1, wherein the amplicon comprises a position 124 bp upstream of the TERT gene transcription start site.

### Claim 4 (depends on 1)

The method of claim 1, wherein a C to T mutation is detected in a nucleotide at position 1,295,228 on the minus strand of chromosome 5 of version hg19 of the human genome sequence.

### Claim 5 (depends on 1)

The method of claim 1, wherein the human subject has been diagnosed with bladder cancer prior to collection of the urine sample.

### Claim 6 (depends on 1)

The method of claim 1, wherein a bladder cancer has been removed from the human subject prior to collection of the urine sample.

### Claim 7

A method of detecting, a somatic mutation and treating bladder cancer in a human subject comprising:
detecting in a nucleic acid obtained from a urine sample of a human the presence of a somatic mutation at position 1,295,228 in the promoter of telomerase reverse transcriptase (TERT) gene on the minus strand of chromosome 5 of version hg19 of the human genome sequence,
wherein the detecting is performed by amplifying a nucleic acid sequence comprising the TERT promoter, or a portion thereof, to form an amplicon and sequencing the amplicon; and
treating the human subject with the somatic mutation in the TERT gene for bladder cancer by a therapy chosen from chemotherapy, a biological agent, a surgery or a radiation therapy, wherein the human subject has not been previously diagnosed with bladder cancer prior to collection of the urine sample.

### Claim 8 (depends on 7)

The method of claim 7, wherein the somatic mutation is detected in a low-grade (LG) noninvasive urothelial carcinoma; a high-grade (HG) noninvasive urothelial carcinoma or a carcinoma in situ (CIS).

### Claim 9 (depends on 7)

The method of claim 7, wherein the somatic mutation is detected in a papillary lesion or in a flat lesion.

### Claim 10 (depends on 1)

The method of claim 1, wherein the human subject has had surgical excision or other treatment for the bladder cancer prior to collection of the urine sample.

### Claim 11 (depends on 1)

The method of claim 1, wherein the detecting is used to monitor the human subject for recurrence of the bladder cancer.

### Claim 12 (depends on 1)

The method of claim 1, wherein the human subject has not been previously diagnosed with bladder cancer prior to collection of the urine sample.

### Claim 13 (depends on 1)

The method of claim 1, wherein the therapy is prescribed by a medical practitioner after the somatic mutation is detected.

### Claim 14 (depends on 7)

The method of claim 7, wherein the therapy is prescribed by a medical practitioner after the somatic mutation is detected.