Kokko Antti, Laiho Päivi, Lehtonen Rainer, Korja Sanna, Carvajal-Carmona Luis G, Järvinen Heikki, Mecklin Jukka-Pekka, Eng Charis, Schleutker Johanna, Tomlinson Ian P M, Vahteristo Pia, Aaltonen Lauri A
Department of Medical Genetics, Molecular and Cancer Biology Research Program, P,O, BOX 63, 00014 University of Helsinki, Finland.
BMC Cancer. 2006 Jun 1;6:145. doi: 10.1186/1471-2407-6-145.
Ephrin receptor B2 (EPHB2) has recently been proposed as a novel tumor suppressor gene in colorectal cancer (CRC). Inactivation of the gene has been shown to correlate with progression of colorectal tumorigenesis, and somatic mutations have been reported in both colorectal and prostate tumors.
Here we have analyzed the EPHB2 gene for germline alterations in 101 individuals either with 1) CRC and a personal or family history of prostate cancer (PC), or 2) intestinal hyperplastic polyposis (HPP), a condition associated with malignant degeneration such as serrated adenoma and CRC.
Four previously unknown missense alterations were observed, which may be associated with the disease phenotype. Two of the changes, I361V and R568W, were identified in Finnish CRC patients, but not in over 300 Finnish familial CRC or PC patients or more than 200 population-matched healthy controls. The third change, D861N, was observed in a UK HPP patient, but not in additional 40 UK HPP patients or in 200 UK healthy controls. The fourth change R80H, originally identified in a Finnish CRC patient, was also found in 1/106 familial CRC patients and in 9/281 healthy controls and is likely to be a neutral polymorphism.
We detected novel germline EPHB2 alterations in patients with colorectal tumors. The results suggest a limited role for these EPHB2 variants in colon tumor predisposition. Further studies including functional analyses are needed to confirm this.
最近，Ephrin受体B2（EPHB2）被认为是结直肠癌（CRC）中的一种新型肿瘤抑制基因。该基因的失活已被证明与结直肠癌发生的进展相关，并且在结直肠癌和前列腺癌中均有体细胞突变的报道。
在此，我们分析了101例个体的EPHB2基因种系改变，这些个体包括：1）患有CRC且有个人或家族前列腺癌（PC）病史的患者；2）肠道增生性息肉病（HPP）患者，这是一种与锯齿状腺瘤和CRC等恶性退变相关的疾病。
观察到四个先前未知的错义改变，这些改变可能与疾病表型相关。其中两个改变，I361V和R568W，在芬兰CRC患者中被鉴定出，但在300多名芬兰家族性CRC或PC患者以及200多名与人群匹配的健康对照中未发现。第三个改变，D861N，在一名英国HPP患者中观察到，但在另外40名英国HPP患者或200名英国健康对照中未发现。第四个改变R80H最初在一名芬兰CRC患者中被鉴定出，在1/106家族性CRC患者和9/281健康对照中也被发现，可能是一种中性多态性。
我们在结直肠肿瘤患者中检测到新的EPHB2基因种系改变。结果表明这些EPHB2变体在结肠肿瘤易感性中的作用有限。需要进一步的研究，包括功能分析，以证实这一点。
