Boparai Karam S, Dekker Evelien, Van Eeden Susanne, Polak Mirjam M, Bartelsman Joep F W M, Mathus-Vliegen Elisbeth M H, Keller Josbert J, van Noesel Carel J M
Department of Gastroenterology & Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
Gastroenterology. 2008 Dec;135(6):2014-8. doi: 10.1053/j.gastro.2008.09.020. Epub 2008 Sep 20.
BACKGROUND & AIMS: MYH-associated polyposis (MAP) is a disorder caused by a bi-allelic germline MYH mutation, characterized by multiple colorectal adenomas. These adenomas typically harbor G:C-->T:A transversions in the APC and K-ras genes caused by MYH deficiency. Occasional hyperplastic polyps (HPs) have been described in MAP patients but a causal relationship has never been investigated. We examined the presence of HPs and sessile serrated adenomas (SSAs) in 17 MAP patients and studied the occurrence of G:C-->T:A transversions in the APC and K-ras gene in these polyps.
MAP patients were analyzed for the presence of HPs/SSAs. APC-mutation cluster region and K-ras codon 12 mutation analysis was performed in adenomas (n = 22), HPs (n = 63), and SSAs (n = 10) from these patients and from a control group of sporadic adenomas (n = 17), HPs (n = 24), and SSAs (n = 17).
HPs/SSAs were detected in 8 of 17 (47%) MAP patients, of whom 3 (18%) met the criteria for hyperplastic polyposis syndrome. APC mutations were detected only in adenomas and comprised exclusively G:C-->T:A transversions. K-ras mutations were detected in 51 of 73 (70%) HPs/SSAs in MAP patients, compared with 7 of 41 (17%) sporadic HPs/SSAs in the control group (P < .0001). In HPs/SSAs, 48 of 51 (94%) K-ras mutations showed G:C-->T:A transversions, compared with 2 of 7 (29%) sporadic HPs/SSAs in the control group (P < .0001).
HPs and SSAs are a common finding in MAP patients. The detection of almost exclusively G:C-->T:A transversions in the K-ras gene of HPs/SSAs strongly suggests that these polyps are related causally to MYH deficiency. This implies that distinct pathways, that is, APC-gene related in adenomas and nonrelated in HPS/SSAs, appear to be operational in MAP.
MYH相关性息肉病（MAP）是一种由双等位基因种系MYH突变引起的疾病，其特征为多发性结直肠腺瘤。这些腺瘤通常因MYH缺陷而在APC和K-ras基因中存在G:C→T:A颠换。MAP患者中偶尔会出现增生性息肉（HP），但尚未对其因果关系进行研究。我们检查了17例MAP患者中HP和无蒂锯齿状腺瘤（SSA）的存在情况，并研究了这些息肉中APC和K-ras基因G:C→T:A颠换的发生情况。
对MAP患者进行HP/SSA检查。对这些患者以及散发性腺瘤（n = 17）、HP（n = 24）和SSA（n = 17）的对照组中的腺瘤（n = 22）、HP（n = 63）和SSA（n = 10）进行APC突变簇区域和K-ras密码子12突变分析。
17例MAP患者中有8例（47%）检测到HP/SSA，其中3例（18%）符合增生性息肉病综合征标准。APC突变仅在腺瘤中检测到，且均为G:C→T:A颠换。MAP患者中73例HP/SSA中有51例（70%）检测到K-ras突变，而对照组41例散发性HP/SSA中有7例（17%）检测到K-ras突变（P <.0001）。在HP/SSA中，51例K-ras突变中有48例（94%）表现为G:C→T:A颠换，而对照组7例散发性HP/SSA中有2例（29%）表现为G:C→T:A颠换（P <.0001）。
HP和SSA在MAP患者中很常见。HP/SSA的K-ras基因中几乎均检测到G:C→T:A颠换，强烈提示这些息肉与MYH缺陷存在因果关系。这意味着在MAP中存在不同的途径，即腺瘤中与APC基因相关，而在HP/SSA中不相关。
