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头颈癌的遗传进展模型:对场癌化的启示。

Genetic progression model for head and neck cancer: implications for field cancerization.

作者信息

Califano J, van der Riet P, Westra W, Nawroz H, Clayman G, Piantadosi S, Corio R, Lee D, Greenberg B, Koch W, Sidransky D

机构信息

Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Hospital, Baltimore, Maryland 21205-2195, USA.

出版信息

Cancer Res. 1996 Jun 1;56(11):2488-92.

PMID:8653682
Abstract

A genetic progression model of head and neck squamous cell carcinoma has not yet been elucidated, and the genetic basis for "field cancerization" of the aerodigestive tract has also remained obscure. Eighty-seven lesions of the head and neck, including preinvasive lesions and benign lesions associated with carcinogen exposure, were tested using microsatellite analysis for allelic loss at 10 major chromosomal loci which have been defined previously. The spectrum of chromosomal loss progressively increased at each histopathological step from benign hyperplasia to dysplasia to carcinoma in situ to invasive cancer. Adjacent areas of tissue with different histopathological appearance shared common genetic changes, but the more histopathologically advanced areas exhibited additional genetic alterations. Abnormal mucosal cells surrounding preinvasive and microinvasive lesions shared common genetic alterations with those lesions and thus appear to arise from a single progenitor clone. Based on these findings, the local clinical phenomenon of field cancerization seems to involve the expansion and migration of clonally related preneoplastic cells.

摘要

头颈部鳞状细胞癌的基因进展模型尚未阐明,而消化道“场癌化”的遗传基础也一直不明。对87个头颈部病变,包括癌前病变以及与致癌物暴露相关的良性病变,使用微卫星分析检测了先前已定义的10个主要染色体位点的等位基因缺失情况。从良性增生到发育异常,再到原位癌和浸润癌,在每个组织病理学阶段,染色体缺失的范围都逐渐增加。具有不同组织病理学表现的相邻组织区域共享共同的基因变化,但组织病理学进展越明显的区域表现出更多的基因改变。癌前病变和微浸润性病变周围的异常黏膜细胞与这些病变共享共同的基因改变,因此似乎起源于单个祖细胞克隆。基于这些发现,场癌化的局部临床现象似乎涉及克隆相关的癌前细胞的扩增和迁移。

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