近日，英國(guó)諾丁漢大學(xué)研究人員發(fā)現(xiàn)腦癌3套遺傳標(biāo)記物,，可能為致命的腦瘤診斷帶來新的希望。
這項(xiàng)最新研究由Richard Grundy教授率領(lǐng),，發(fā)表在權(quán)威雜志Lancet Oncology最新一期上,。
盡管需要新的、更有效的治療手段,，早些年也已經(jīng)開展了一系列研究,，但取得的成績(jī)并不如人意。這項(xiàng)諾丁漢大學(xué)完成的研究旨在篩選出可用來提高癌癥治療功效和開展治療的分子標(biāo)記物,。
諾丁漢大學(xué)與加拿大多倫多病童醫(yī)院合作共收集到142例中樞神經(jīng)系統(tǒng)PNET的樣品,。Richard Grundy教授說：我們先前的研究使得我們意識(shí)到需要國(guó)際努力才能帶來足夠數(shù)量樣本，才能使我們更好地了解這種疾病,。
通過研究腫瘤的基因,，他們發(fā)現(xiàn)該類型腫瘤有三個(gè)子類型具有明顯的遺傳異常，這些基因的異?？蓪?dǎo)致患者出現(xiàn)不同的結(jié)果,。
他們發(fā)現(xiàn)通過在兩個(gè)遺傳標(biāo)記物（LIN28和OLIG2）表達(dá)上的差異，每個(gè)基因組都有自己的基因特征,。
當(dāng)與臨床因素包括年齡,、生存期和轉(zhuǎn)移相比時(shí)，他們發(fā)現(xiàn)第1腫瘤組患者往往是最年輕的患者,，存活率也最低,。而第3組腫瘤患者在診斷時(shí)出現(xiàn)轉(zhuǎn)移的發(fā)病率時(shí)最高的。
最終,，研究確定了兩個(gè)遺傳標(biāo)記物L(fēng)IN28和OLIG2可能是腦腫瘤患者的診斷和預(yù)測(cè)的潛在標(biāo)志物,。
這項(xiàng)研究由加拿大健康研究學(xué)院、Brainchild/Sick Kids基金會(huì)和Samantha Dickson腦腫瘤信托基金資助,。（生物谷：Bioon.com）
doi:10.1016/S1470-2045(12)70257-7
PMC:
PMID:
Markers of survival and metastatic potential in childhood CNS primitive neuro-ectodermal brain tumours: an integrative genomic analysis
Daniel Picard BSc a *, Suzanne Miller PhD d *, Cynthia E Hawkins MD b, Prof Eric Bouffet MD a, Hazel A Rogers PhD d, Tiffany SY Chan BSc a, Seung-Ki Kim MD e, Prof Young-Shin Ra MD f, Jason Fangusaro MD g, Andrey Korshunov MD h, Helen Toledano MD i, Hideo Nakamura MD j, James T Hayden MD k, Jennifer Chan MD l, Lucie Lafay-Cousin MD m, Pingzhao Hu PhD c, Xing Fan MD n, Prof Karin M Muraszko MD n, Prof Scott L Pomeroy MD o, Ching C Lau MD p, Prof Ho-Keung Ng MD q, Chris Jones PhD r, Timothy Van Meter PhD s, Prof Steven C Clifford PhD k, Prof Charles Eberhart MD t, Amar Gajjar MD u, Stefan M Pfister MD v, Prof Richard G Grundy MD d , Dr Annie Huang MD
Background
Childhood CNS primitive neuro-ectodermal brain tumours (PNETs) are very aggressive brain tumours for which the molecular features and best treatment approaches are unknown. We assessed a large cohort of these rare tumours to identify molecular markers to enhance clinical management of this disease.
Methods
We obtained 142 primary hemispheric CNS PNET samples from 20 institutions in nine countries and examined transcriptional profiles for a subset of 51 samples and copy number profiles for a subset of 77 samples. We used clustering, gene, and pathway enrichment analyses to identify tumour subgroups and group-specific molecular markers, and applied immunohistochemical and gene-expression analyses to validate and assess the clinical significance of the subgroup markers.
Findings
We identified three molecular subgroups of CNS PNETs that were distinguished by primitive neural (group 1), oligoneural (group 2), and mesenchymal lineage (group 3) gene-expression signatures with differential expression of cell-lineage markers LIN28 and OLIG2. Patients with group 1 tumours were most often female (male:female ratio 0·61 for group 1 vs 1·25 for group 2 and 1·63 for group 3; p=0·043 [group 1 vs groups 2 and 3]), youngest (median age at diagnosis 2·9 years [95% CI 2·4—5·2] for group 1 vs 7·9 years [6·0—9·7] for group 2 and 5·9 years [4·9—7·8] for group 3; p=0·005), and had poorest survival (median survival 0·8 years [95% CI 0·5—1·2] in group 1, 1·8 years [1·4—2·3] in group 2 and 4·3 years [0·8—7·8] in group 3; p=0·019). Patients with group 3 tumours had the highest incidence of metastases at diagnosis (no distant metastasis:metastasis ratio 0·90 for group 3 vs 2·80 for group 1 and 5·67 for group 2; p=0·037).
Interpretation
LIN28 and OLIG2 are promising diagnostic and prognostic molecular markers for CNS PNET that warrant further assessment in prospective clinical trials.
