Mutations in pancreatic neoplasms

Patent metadata

Field	Value
Publication number	US-9976184-B2
Application number	US-201214128478-A
Country	US
Kind code	B2
Filing date	Jun 22, 2012
Priority date	Jun 23, 2011
Publication date	May 22, 2018
Grant date	May 22, 2018

Abstract

To help reveal the pathogenesis of these lesions, we purified the DNA from Intraductal Papillary Mucinous Neoplasm (IPMN) cyst fluids from 19 patients and searched for mutations in 169 genes commonly altered in human cancers. We identified recurrent mutations at codon 201 of GNAS. We found that GNAS mutations were present in 66% of IPMNs and that either KRAS or GNAS mutations could be identified in 96%. In eight cases, we could investigate invasive adenocarcinomas that developed in association with IPMNs containing GNAS mutations. In seven of these eight cases, the GNAS mutations present in the IPMNs were also found in the invasive lesion. GNAS mutations were not found in other types of cystic neoplasms of the pancreas or in invasive adenocarcinomas not associated with IPMNs. These data suggest that GNAS mutations can inform the diagnosis and management of patients with cystic pancreatic lesions.

First claim

The invention claimed is:

1. A method comprising the steps of:
testing a sample comprising nucleic acids from pancreatic cyst fluid or pancreatic cyst wall tissue;
detecting in the sample comprising nucleic acids a histidine or cysteine codon at codon 201 in GNAS;
determining that the sample comprises a pancreatic intraductal papillary mucinous neoplasm (IPMN) when the histidine or cysteine codon is detected; and
performing surgery to remove the IPMN.

2. The method of claim 1 further comprising the step of:
detecting in the sample comprising nucleic acids an aspartic acid, valine, or arginine codon at codon 12 in KRAS.

3. The method of claim 1 , wherein the sample is from pancreatic cyst fluid.

4. The method of claim 2 , wherein the sample is from pancreatic cyst fluid.

5. The method of claim 1 , wherein a histidine codon at codon 201 in GNAS is detected.

6. The method of claim 1 , wherein a cysteine codon at codon 201 in GNAS is detected.

7. The method of claim 2 , wherein an aspartic acid codon at codon 12 in KRAS is detected.

8. The method of claim 2 , wherein a valine codon at codon 12 in KRAS is detected.

9. The method of claim 2 , wherein a arginine codon at codon 12 in KRAS is detected.

10. The method of claim 1 wherein the sample is obtained by endoscopic ultrasound (EUS).

11. The method of claim 1 wherein:
the sample is from pancreatic cyst wall tissue.

12. The method of claim 11 , wherein a histidine codon at codon 201 in GNAS is detected.

13. The method of claim 11 , wherein a cysteine codon at codon 201 in GNAS is detected.

14. The method of claim 11 wherein the sample is obtained by endoscopic ultrasound (EUS).

15. A method comprising the steps of:
testing a sample comprising nucleic acids from pancreatic ductal adenocarcinoma tissue;
detecting in the sample comprising nucleic acids a histidine or cysteine codon at codon 201 in GNAS; and
performing surgery to remove the pancreatic ductal adenocarcinoma when the cysteine or histidine codon is detected.

16. The method of claim 15 , wherein a histidine codon at codon 201 in GNAS is detected.

17. The method of claim 15 , wherein a cysteine codon at codon 201 in GNAS is detected.

18. The method claim 15 wherein the sample is obtained by endoscopic ultrasound (EUS).

19. A method comprising the steps of:
testing a sample comprising nucleic acids from a patient, wherein said sample is selected from the group consisting of pancreatic juice and stool;
detecting in the sample comprising nucleic acids a cysteine or histidine codon at codon 201 in GNAS;
determining that the patient has a pancreatic intraductal papillary mucinous neoplasm (IPMN) when the cysteine or histidine codon is detected; and
performing surgery on the patient to remove the IPMN.

20. The method of claim 19 further comprising:
detecting in the sample comprising nucleic acids an aspartic acid, valine, or arginine codon at codon 12 in KRAS.

21. The method of claim 19 further comprising:
examining the patient to detect the presence of a pancreatic tumor.

22. The method of claim 20 further comprising:
examining the patient to detect the presence of a pancreatic tumor.

Assignees

• Vogelstein Bert
• Kinzler Kenneth W
• Wu Jian
• Diaz Luis
• Papadopoulos Nickolas
• Matthaei Hanno
• Hruban Ralph
• Maitra Anirban
• Univ Johns Hopkins

Inventors

• Vogelstein Bert
• Kinzler Kenneth W
• Wu Jian
• Diaz Luis
• Papadopoulos Nickolas
• Matthaei Hanno
• Hruban Ralph
• Maitra Anirban

Classifications

• C12Q2600/112

  Disease subtyping, staging or classification · CPC title

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• C12Q1/6886 Primary

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