Gene amplification of ESR1 in breast cancers-fact or fiction? A fluorescence in situ hybridization and multiplex ligation-dependent probe amplification study
スポンサーリンク
概要
- 論文の詳細を見る
Oestrogen receptor-alpha (ERα), encoded by the ESR1 gene located on 6q25, is a nuclear transcription factor. Since it was reported in 2007 that more than 20% of breast cancers show ESR1 gene amplification, there has been considerable controversy about its frequency and clinical significance. We set out to assess the frequency and levels of ESR1 amplification in breast cancers. In a total of 106 breast needle biopsy specimens examined by immunohistochemistry, 78 tumours contained more than 10% ERα-positive cancer cells. In fluorescence in situ hybridization (FISH) analysis with an ESR1-specific probe, variously extended ESR1 signals were found in ERα-expressing cells. Some of these were indistinguishable from large clustered signals generally accepted to mean high-level gene amplification in homogeneously staining regions (HSRs), and could be considered to represent gene amplification. However, with RNase treatment, the 'HSR-like' signals changed to small compact signals, and are thus thought to represent concentrated RNA. FISH using two differently labelled probes corresponding to the non-overlapping 5'- and 3'-end portions of the ESR1 gene on touch smears showed a preserved spatial relationship of the 3' to 5' sequence of ESR1, therefore strongly suggesting that the RNA consisted of primary transcripts. Using touch smears obtained from 51 fresh tumours, precise enumeration of ESR1 signals with a correction by the number of centromere 6 on FISH after RNase A treatment revealed that three tumours (5.9%) had tumour cells with one to three additional copies of ESR1 as predominant subpopulations. This infrequent and low level of gene amplification of ESR1 was also detected as a 'gain' of the gene by analysis with multiplex ligation-dependent probe amplification (MLPA). The consistent results from immunohistochemistry, FISH, and MLPA in the present study settle the long-standing debate concerning gene amplification of ESR1 in breast carcinoma. © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
論文 | ランダム
- 人工肺
- DNAシーケンシング (特集 国立遺伝学研究所60年の歩みを映して) -- (共同利用機関として--頼りにされる遺伝研)
- 出張報告 深まる日中省エネ・環境ビジネスの可能性(重慶市)
- Internal Auditor 1996年2月号より うまく書いてもウマくいかない時--文章も上手なキレ者内部監査人も監査報告書の筆致が狂えばトラブル必至
- キリストの証人 : 神学部チャペルにおける講演