# US 10,370,715 B2 · Methods for identifying, diagnosing, and predicting survival of lymphomas

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- Number: US 10,370,715 B2
- Document ID: US10370715B2
- Status: Granted
- Kind: B2
- Application number: 14/570,316
- Filed: 2014-12-15
- Published: 2015-06-18
- Granted: 2019-08-06
- Earliest claimed: 2003-09-03
- Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services
- Applicants: The United States of America, as represented by the Secretary, Department of Health and Human Services
- Inventors: Louis M. Staudt; George W. Wright; Sandeep Dave; Bruce K. Tan
- Web page: https://patentgrep.com/patent/US10370715B2

## CPC

- C12Q 1/6883: for diseases caused by alterations of genetic material
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- G01N 33/57557: {of other specific parts of the body, e.g. brain}
- C12Q 2600/112: Disease subtyping, staging or classification
- C12Q 2600/118: Prognosis of disease development
- C12Q 2600/158: Expression markers
- G01N 2800/60: Complex ways of combining multiple protein biomarkers for diagnosis
- 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

The invention provides methods for identifying, diagnosing, and predicting survival in a lymphoma or lymphoproliferative disorder on the basis of gene expression patterns. The invention provides a microarray for obtaining gene expression data from a lymphoma sample. The invention also provides a variety of methods for utilizing lymphoma gene expression data to determine the identity of a particular lymphoma and to predict survival in a subject diagnosed with a particular lymphoma, which is useful in developing an appropriate therapeutic approach.

## Claims

### Claim 1

A method of treating a subject suffering from diffuse large B cell lymphoma (DLBCL), the method comprising:
(1) determining a first survival predictor score for the subject comprising the steps of a) through f:
a) isolating gene expression product from a biopsy sample from the subject;
b) obtaining gene expression data from the isolated gene expression product by detecting expression levels for genes in an ABC DLBCL high gene expression signature, a lymph node gene expression signature, and an MHC class II gene expression signature;
c) obtaining an average gene expression level for the genes in the ABC DLBCL high gene expression signature to thereby obtain an ABC DLBCL high gene expression signature value;
d) obtaining an average gene expression level for the genes in the lymph node gene expression signature to thereby obtain a lymph node gene expression signature value;
e) obtaining an average gene expression level for the genes in the MHC class II gene expression signature to thereby obtain an MHC class II gene expression signature value; and
f) calculating a survival predictor score using an equation: [0.586*(ABC DLBCL high gene expression signature value)] - [0.468*(lymph node gene expression signature value)] - [0.336*(MHC class II gene expression signature)];
wherein a higher survival predictor score is associated with worse survival;
(2) determining a second survival predictor score for the subject comprising the steps of a) through f) of (1);
(3) comparing the first and second survival predictor scores of (1) and (2);
(4) determining the subject has a poor prognosis by determining the second survival predictor score is higher than the first survival predictor score; and
(5) treating the subject.

### Claim 2 (depends on 1)

The method of claim 1 wherein the step of obtaining gene expression data comprises use of a microarray.

### Claim 3 (depends on 1)

The method of claim 1 wherein the ABC DLBCL gene expression signature comprises at least one gene selected from the group consisting of (listed by UNIQID): 1134271, 1121564, 1119889, 1133300, 1106030, 1139301, 1122131, 1114824, 1100161, and 1120129.

### Claim 4 (depends on 1)

The method of claim 1 wherein the lymph node gene expression signature comprises at least one gene selected from the group consisting of (listed by UNIQID): 1097126, 1120880, 1098898, 1123376, 1128945, 1130994, 1124429, 1099358, 1130509, 1095985, 1123038, 1133700, 1122101, and 1124296.

### Claim 5 (depends on 1)

The method of claim 1 wherein the MHC class II gene expression signature comprises at least one gene selected from the group consisting of (listed by UNIQID): 1123127, 1136777, 1137771, 1134281, 1136573, and 1132710.