Choi Mi Ryoung, An Chang Hyeok, Chung Yeun Jun, Choi Youn Jin, Yoo Nam Jin, Lee Sug Hyung
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
APMIS. 2014 Dec;122(12):1207-12. doi: 10.1111/apm.12286. Epub 2014 Jun 7.
ERBB3 is a member of EGFR family receptor tyrosine kinases, genetic alterations of which are common and therapeutically targeted in human cancers. Recently, somatic mutations of ERBB3 gene, including recurrent mutation in exon 3 altering Val104, were reported in gastric cancers (GC) and colorectal cancers (CRC), strongly suggesting its role in the development of GC and CRC. To examine whether the recurrent ERBB3 mutations of exon 3 occur in GC and CRC, and other malignancies as well, we analyzed the ERBB3 in 1677 cancer tissues by a single-strand conformation polymorphism (SSCP) assay. We identified ERBB3 mutations altering the Val104 mutations in GC (0.5%) and CRC (2.2%). However, we did not find the ERBB3 mutations in the other cancers besides GC and CRC. We observed that an increased intensity of phosphorylated ERBB3 (pERBB3) in GC and CRC. Of note, all of the cancers with ERBB3 mutations displayed an increased intensity of pERBB3 immunostaining. Our data indicate that the recurrent ERBB3 mutations altering Val104 occur predominantly in GC and CRC. Also, the data suggest that ERBB3 is altered in GC and CRC by various ways, including somatic mutations and increased expression that might play roles in tumorigenesis.
ERBB3是表皮生长因子受体（EGFR）家族受体酪氨酸激酶的成员之一，其基因改变在人类癌症中很常见且是治疗靶点。最近，在胃癌（GC）和结直肠癌（CRC）中报道了ERBB3基因的体细胞突变，包括第3外显子中改变Val104的复发性突变，这强烈表明其在GC和CRC发生发展中的作用。为了研究第3外显子的ERBB3复发性突变是否也存在于GC、CRC及其他恶性肿瘤中,我们通过单链构象多态性（SSCP）分析检测了1677例癌组织中的ERBB3。我们在GC（0.5%）和CRC（2.2%）中发现了改变Val104的ERBB3突变。然而，除了GC和CRC，我们在其他癌症中未发现ERBB3突变。我们观察到GC和CRC中磷酸化ERBB3（pERBB3）强度增加。值得注意的是，所有发生ERBB3突变的癌症均显示pERBB3免疫染色强度增加。我们的数据表明，改变Val104的ERBB3复发性突变主要发生在GC和CRC中,。此外,数据表明，ERBB3在GC和CRC中以多种方式改变，包括体细胞突变和表达增加，这可能在肿瘤发生中起作用。
