抽象
alk.,ROS1.和RET重新排列can also be diagnosed in asbestos-related lung cancershttp://ow.ly/rFpb30hV5Wt
To the Editor:
Lung cancer remains the main cause of cancer death. In addition to smoking, exposure to occupational carcinogens constitutes a major risk for lung cancer. Among occupational cancers, asbestos-related ones are the most frequent, accounting for about 5–7% of lung cancers. A better understanding of the molecular pathways implicated in the progression of cancer has greatly improved the therapeutic management of patients with advanced lung cancers, especially nonsmall cell lung cancer (NSCLC) of the adenocarcinoma subtype. Indeed, several therapies targeting the epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)/ROS1 pathways are now approved to treat patients with advancedEGFR.- 被隔绝或ALK / ROS1.- 分别为NSCLC。而EGFR.和alk.改变主要是遇到非非小细胞肺癌smokers, other biomarkers are more frequent in smoking patients, such as克拉斯mutations, and are of prognostic interest. Nevertheless, the frequencies of the different biomarkers analysed daily for the therapeutic management of patients with NSCLC are rarely reported in occupational lung cancers, including asbestos-related ones.
The study by Paris.等。[1] of the frequencies ofEGFR,ALK,KRAS,HER2,BRAF和Pik3.肺癌和职业暴露于包括石棉的肺癌和职业接触的分子改变是非常有趣的。然而,除了p未研究其他也是治疗兴趣的其他生物标志物aris.等。[1], 如ROS1,RET,NTRK1和遇见。我们还刚刚进行了一项专注于致癌患者的致癌染色体重排,其在经济补偿的石棉相关肺癌的群体中。在这里,我们打算展示我们单眼回顾性研究的结果。
在以前的工作中,我们在2003年至2013年期间,我们报告了我们职业病中心的经济补偿的石棉有关的肺癌146名患者的临床,职业和组织病理学特征[2]。As an extension of this study and after approval by our institutional review board (CHRU Brest 2016.CE10), we collected formalin-fixed, paraffin-embedded tumour samples to perform additional molecular analyses in 56 patients (for 90 patients, no tumour sample was available at the time of our retrospective study). We performed not only ALK analyses, as reported by Paris.等。[1],使用免疫组织化学(5A4克隆;临床,楠庭,法国)和荧光原位杂交(鱼类)分析(种子LSI ALK双色分裂除去鱼探针;雅培分子,润滑者,法国),但也是ROS1分析(免疫组织化学与克隆D4D6(细胞信号传导技术; Ozyme,Saint Quentin EN Yvelines,France)和鱼类与群体如前所述,6Q22 ROS1分开了鱼探针套件(雅培分子)[3,4]。使用鱼,我们也搜索了RET和神经营养ntrk1.重排(RET(10Q11)突破(Kreatech / Leica,Nanterre,France)和Zytolight Spec Ntrk1双色分开探头(Zytovision GmbH,Bremerhaven,Germany)以及遇见扩增(产物LSI D7S486(7Q31)光谱法/流体CEP 7 Spectrumgreen探针,雅培分子)。
在56个肿瘤中,32个是腺癌,20个是鳞状细胞癌,4个是小细胞癌。与P研究相比的主要差异aris.等。[1所有患者都是男性,而不是队伍仅代表了我们的队列中的五(9%)患者。四种(7%)患者的肺腺癌遇到致癌染色体重排:两个alk.-rearranged tumours (with positive immunohistochemistry and FISH results) in a never-smoker and a 20-pack-year smoker, oneROS1.- 在10包吸烟者(阳性免疫组化和鱼类结果)和一个RET- 在20包吸烟者(正鱼片结果)中的肿瘤。没有ntrk1.rearrangement or遇见诊断扩增。
Tobacco and asbestos are known to have synergistic carcinogenic effects, with 10- and five-fold increased risks of lung cancer, respectively, if considered separately, and a 50-fold increased risk in patients with both exposures. Albeit that oncogenic rearrangements are classically described in NSCLC of young and never-smoking patients, we regularly diagnosealk.重新排列in patients with a smoking history [4]。Asbestos is known to cause recurrent chromosomal aberrations in lung cancers (例如在2P16,9Q33.1和19P13基因座中)[5]。除了染色体增益和损失之外,在很少的情况下检测到导致治疗相关性的基因融合或扩增的染色体改变(alk.,2p23轨迹)否学习(ROS1.,6q22.1基因座; RET, 10q11.21 locus;ntrk1., 1q23.1 locus;c-met.7q31.2基因座在石棉相关的肺癌中。在P的研究中aris.等。[1],21名石棉患者中没有一个有过alk.-Rearranged癌症[1]。In our study, we have demonstrated that chromosomal alterations of theranostic relevance are rare but can be encountered among patients with asbestos-related lung cancers, among smokers and nonsmokers, opening potential access to targeted therapies for these patients.
In our study, having considered only patients with financially compensated asbestos-related lung cancers constitutes a bias preventing any estimation of the frequency of chromosomal rearrangements among asbestos-related lung cancers. In a future work, it would be interesting (and may be feasible in the cohort of Paris.等。[1])分析ROS1,RET,NTRK1和遇见在较大的石棉队列,暴露的永不吸烟者中进一步研究了石棉暴露与治疗患者的染色体畸变之间的关系。
Acknowledgements
We would like to also acknowledge the pathologists of Brest and the Local tumor tissue biobank BB-0033-00037 (“CRB Santé/Tumorothèque de Brest”) for their collaboration in this study and Miss Sandrine Duigou, Mrs Le Prunennec Annette and Mr Eric Gobin for technical assistance.
脚注
支持声明:这项研究得到了La Ligue Contre Le Cancer CD29的支持。本文的资金信息已存入CrossRef Resder注册表。
Conflict of interest: None declared.
- 收到December 15, 2017.
- Accepted2017年12月30日。
- 版权所有©ers 2018