公开(公告)号：WO2012178034A3

公开(公告)日：2012-12-27

申请号：PCT/US2012/043783

申请日：2012-06-22

Applicant: THE JOHNS HOPKINS UNIVERSITY ,  VOGELSTEIN, Bert ,  KINZLER, Kenneth W. ,  WU, Jian ,  DIAZ, Luis ,  PAPADOPOULOS, Nickolas ,  MATTHAEI, Hanno ,  HRUBAN, Ralph ,  MAITRA, Anirban

Inventor： VOGELSTEIN, Bert ,  KINZLER, Kenneth W. ,  WU, Jian ,  DIAZ, Luis ,  PAPADOPOULOS, Nickolas ,  MATTHAEI, Hanno ,  HRUBAN, Ralph ,  MAITRA, Anirban

IPC: C12Q1/68 ,  C12N15/11

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.

公开(公告)号：WO2012178034A2

公开(公告)日：2012-12-27

申请号：PCT/US2012043783

申请日：2012-06-22

Applicant: UNIV JOHNS HOPKINS ,  VOGELSTEIN BERT ,  KINZLER KENNETH W ,  WU JIAN ,  DIAZ LUIS ,  PAPADOPOULOS NICKOLAS ,  MATTHAEI HANNO ,  HRUBAN RALPH ,  MAITRA ANIRBAN

Inventor： VOGELSTEIN BERT ,  KINZLER KENNETH W ,  WU JIAN ,  DIAZ LUIS ,  PAPADOPOULOS NICKOLAS ,  MATTHAEI HANNO ,  HRUBAN RALPH ,  MAITRA ANIRBAN

IPC: C12Q1/68 ,  C12N15/11

CPC classification number: C12Q1/6886 ,  C12Q2600/112 ,  C12Q2600/156

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.

Abstract translation: 为了揭示这些病变的发病机制，我们从19名患者的导管内乳头状粘液性肿瘤（IPMN）囊肿液中纯化DNA，并搜索了在人类癌症中通常改变的169种基因中的突变。 我们在GNAS的201号密码子处鉴定了复发性突变。 我们发现GNAS突变存在于66％的IPMNs中，KRAS或GNAS突变可以在96％中鉴定。 在8例中，我们可以研究与含有GNAS突变的IPMN相关的侵袭性腺癌。 在这8例中有7例中，存在于IPMNs中的GNAS突变也在侵袭性损伤中发现。 在其他类型的胰腺囊性肿瘤或与IPMN无关的侵袭性腺癌中未发现GNAS突变。 这些数据表明，GNAS突变可以为囊性胰腺病变患者的诊断和治疗提供依据。