Global genomic analysis of intraductal papillary mucinous neoplasms of the pancreas reveals significant molecular differences compared to ductal adenocarcinoma.
Global genomic analysis of intraductal papillary mucinous neoplasms of the pancreas reveals significant molecular differences compared to ductal adenocarcinoma.
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DOI：
10.1097/sla.0b013e31819a6e16
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发表时间：
2009-03
影响因子：
9
通讯作者：
Iafrate AJ
中科院分区：
文献类型：
--
作者：
Fritz S;Fernandez-del Castillo C;Mino-Kenudson M;Crippa S;Deshpande V;Lauwers GY;Warshaw AL;Thayer SP;Iafrate AJ
目的：探讨胰腺导管内乳头状黏液性肿瘤(IPMN)与导管腺癌(PDAC)是否具有不同的遗传背景。IPMN和IPMN相关腺癌的生物学和临床行为不同于PDAC，其肿瘤生长侵袭性较小，显著提高了生存率。到目前为止，IPMN临床行为的分子机制还不完全清楚。在2年的病程中，前瞻性地发现了128个囊性胰腺病变。从相应的手术标本中分离出57个IPMN，并根据组织学标准将其细分为低度不典型增生、中度不典型增生、高度不典型增生和浸润性癌。20个样本适合于DNA提取和后续阵列CGH的执行。低级别异型增生的IPMN中无一例出现可检测到的染色体异常，而中、重度异型增生的IPMN则表现出频繁的拷贝数改变。常见的缺失区域位于染色体5q、6q、10q、11q、13q、18q和22q。高度不典型增生或侵袭的IPMN中5q、6q和11q染色体丢失的发生率明显高于PDAC。13个中度异型或恶性的IPMN中有10个存在部分或全部6q染色体缺失，最小缺失区位于线性位78~130.0之间。本研究首次使用阵列计算全息图来表征IPMN。反复出现的细胞遗传学改变与PDAC中描述的不同。阵列CGH可能有助于区分这两个实体，并深入了解它们在生物学和预后方面的差异。
To determine whether intraductal papillary mucinous neoplasms of the pancreas (IPMNs) have a different genetic background compared with ductal adenocarcinoma (PDAC). The biologic and clinical behavior of IPMNs and IPMN-associated adenocarcinomas is different from PDAC in having a less aggressive tumor growth and significantly improved survival. Up to date, the molecular mechanisms underlying the clinical behavior of IPMNs are incompletely understood. 128 cystic pancreatic lesions were prospectively identified during the course of 2 years. From the corresponding surgical specimens, 57 IPMNs were separated and subdivided by histologic criteria into those with low-grade dysplasia, moderate dysplasia, high-grade dysplasia, and invasive cancer. Twenty specimens were suitable for DNA isolation and subsequent performance of array CGH. While none of the IPMNs with low-grade dysplasia displayed detectable chromosomal aberrations, IPMNs with moderate and high-grade dysplasia showed frequent copy number alterations. Commonly lost regions were located on chromosome 5q, 6q, 10q, 11q, 13q, 18q, and 22q. The incidence of loss of chromosome 5q, 6q, and 11q was significantly higher in IPMNs with high-grade dysplasia or invasion compared with PDAC. Ten of 13 IPMNs with moderate dysplasia or malignancy had loss of part or all of chromosome 6q, with a minimal deleted region between linear positions 78.0 and 130.0. This study is the first to use array CGH to characterize IPMNs. Recurrent cytogenetic alterations were identified and were different than those described in PDAC. Array CGH may help distinguish between these 2 entities and give insight into the differences in their biology and prognosis.