Hereditary cancer genes

Patent metadata

Field	Value
Publication number	US-12410478-B2
Application number	US-202117383093-A
Country	US
Kind code	B2
Filing date	Jul 22, 2021
Priority date	Jun 6, 2012
Publication date	Sep 9, 2025
Grant date	Sep 9, 2025

Abstract

The invention generally relates to a molecular classification of disease predisposition and particularly to molecular markers for cancer predisposition and methods of use thereof.

First claim

What is claimed is:

1. A method comprising:
a) extracting genomic DNA from a sample comprising germline cells of a patient;
b) forming a mixture by hybridizing nucleic acid probes that hybridize to the genomic DNA, wherein the genomic DNA comprises a plurality of nucleic acid molecules, wherein said plurality of nucleic acid molecules comprise the coding regions of a plurality of test genes and wherein said plurality of test genes comprise target genes: APC gene, ATM gene, BARD 1 gene, BMPRIA gene, Breast Cancer 1 (BRCA1) gene, Breast Cancer 2 (BRCA2) gene, BRIP1 gene, CDH1 gene, CDK4 gene, CDKN2A gene, CHEK2 gene, EPCAM gene, MLH1 gene, MSH2 gene, MSH6 gene, MUTYH gene, NBN1 gene, PALB2 gene, PMS2 gene, phosphatase and tensin homolog (PTEN) gene, RADSIC gene, RADS1D gene, SMAD4 gene, STK11 gene, and TP53 gene;
c) performing one or more amplification reactions for amplifying said plurality of nucleic acid molecules in the DNA mixture in the presence of one or more primer pairs, wherein each of the primer pairs generates amplification products comprising a portion of each of the target genes;
d) sequencing said amplification products; and
e) comparing the sequences of the amplification products with one or more reference sequences of each of the target genes using an alignment software, thereby determining whether the patient has germline mutations in the target genes based on the presence of at least one insertion or deletion greater than 1,000 nucleotides in the sequences of the amplification products from the plurality of test genes.

2. The method of claim 1 , wherein the one or more reference sequences comprise the sequence of each of the target genes in the following table:

Entrez

Gene

Symbol
SEQ ID NO

APC
 1

ATM
 20

BARD1
 21

BMPR1A
 60

BRCA1
 97

BRCA2
128

BRIP1
158

CDH1
182

CDK4
201

CDKN2A
212

CHEK2
223

EPCAM
244

MLH1
289

MSH2
355

MSH6
374

MUTYH
387

NBN
411

PALB2
430

PMS2
450

PTEN
475

RAD51C
516

RAD51D
521

SMAD4
546

STK11
561

TP53
576.

3. The method of claim 1 , wherein at least one of the amplification products comprises at least a portion of an exon sequence and an intron sequence comprising at least 10 base pairs in length flanking at least one end of said exon sequence.

4. The method of claim 1 further comprising determining if the patient has at least one second level risk factors comprising personal risk factors and family risk factors.

5. The method of claim 4 , wherein the personal risk factors comprise that the patient has a history of multiple primary cancers, a positive triple negative breast cancer, a history of ovarian cancer, a history of smoking, a positive tissue biopsy for a cancer, a positive vaginal pap smear for a cancer, a history of male breast cancer, an enlarged prostate, colon polyps, and an age of the patient if a cancer is diagnosed, an age of menopause of the patient, and an age of menarche of the patient.

6. The method of claim 4 , wherein the family risk factors comprise that the patient has Ashkenazi Jewish ancestry, a relative with early onset cancer, a relative with multiple primary cancers, a relative with male breast cancer, a relative with ovarian cancer, and a relative with triple negative breast cancer.

7. The method of claim 1 , wherein the target genes comprise at least 25% of the plurality of test genes.

8. The method of claim 1 , wherein the target genes comprise at least 50% of the plurality of test genes.

9. The method of claim 1 , wherein the sample is a human sample.

Assignees

• Myriad Genetics Inc

Inventors

• Timms Kirsten
• Allen Brian
• Hartman Anne-Renee

Classifications

• G01N33/57545

  of the ovaries · CPC title

• G01N33/57515

  of the breast · CPC title

• C12Q2600/16

  Primer sets for multiplex assays · CPC title

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• A61K31/138

  Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine (atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377) · CPC title