Perspectives and Issues in the Assessment of SMARCA4 Deficiency in the Management of Lung Cancer Patients.
Perspectives and Issues in the Assessment of SMARCA4 Deficiency in the Management of Lung Cancer Patients.
复制标题
SMARCA 4缺陷在肺癌患者管理中的评估前景和问题。
作者：
Armon S;Hofman P;Ilié M
2020年，肺癌在法国癌症发病率中排名第三，在约85%的非小细胞肺癌中，腺癌是最常见的亚型。用于肺腺癌治疗的分子基因分型技术的不断发展，导致了目前对肿瘤抑制基因的关注，特别是SMARCA4基因的功能缺失突变。smarca4缺陷腺癌在年轻男性吸烟者中以实体形态为主。识别smarca4缺陷腺癌的重要性已经引起了肺癌治疗的兴趣，因为在大多数病例中，它在诊断时具有血管侵入和胸膜转移的侵袭性行为。这些患者的临床结果较差，总体生存率较短，无论疾病处于何种阶段。随着敏感和特异性免疫组织化学抗体的出现，在大多数病理实验室中检测SMARCA4缺陷是可能的。基于当前的下一代测序面板，可以与其他已建立的肺癌分子标记一起检测基因突变。测序还将允许识别相关基因突变，特别是KRAS， KEAP1和STK11，它们对患者的总生存期和无进展生存期有影响。抗pd - l1治疗这种高肿瘤突变负担癌症的预测数据目前尚不确定，需要更多的基础研究。靶标药物的鉴定也仍处于临床前试验阶段。因此，识别smarca4缺陷腺癌是至关重要的，因为尽管患病率非常低，但它对患者生存的影响更大。在此，我们讨论了SMARCA4的病理生理、临床病理后果以及不同的检测方法，强调了评估SMARCA4缺乏对非小细胞肺癌患者治疗的前景和挑战。这是必要的，因为识别与肿瘤抑制基因（如SMARCA4）相关的生物标志物的当代转变是趋势；因此，病理学家和临床医生需要提高对SMARCA4-dNSCLC实体的认识，并对新的管理策略进行密切随访，以克服此类患者生存可能性低的问题。
Lung cancers are ranked third among the cancer incidence in France in the year 2020, with adenocarcinomas being the commonest sub-type out of ~85% of non-small cell lung carcinomas. The constant evolution of molecular genotyping, which is used for the management of lung adenocarcinomas, has led to the current focus on tumor suppressor genes, specifically the loss of function mutation in the SMARCA4 gene. SMARCA4-deficient adenocarcinomas are preponderant in younger aged male smokers with a predominant solid morphology. The importance of identifying SMARCA4-deficient adenocarcinomas has gained interest for lung cancer management due to its aggressive behavior at diagnosis with vascular invasion and metastasis to the pleura seen upon presentation in most cases. These patients have poor clinical outcome with short overall survival rates, regardless of the stage of disease. The detection of SMARCA4 deficiency is possible in most pathology labs with the advent of sensitive and specific immunohistochemical antibodies. The gene mutations can be detected together with other established lung cancer molecular markers based on the current next generation sequencing panels. Sequencing will also allow the identification of associated gene mutations, notably KRAS, KEAP1, and STK11, which have an impact on the overall survival and progression-free survival of the patients. Predictive data on the treatment with anti-PD-L1 are currently uncertain in this high tumor mutational burden cancer, which warrants more groundwork. Identification of target drugs is also still in pre-clinical testing. Thus, it is paramount to identify the SMARCA4-deficient adenocarcinoma, as it carries worse repercussions on patient survival, despite having an exceptionally low prevalence. Herein, we discuss the pathophysiology of SMARCA4, the clinicopathological consequences, and different detection methods, highlighting the perspectives and challenges in the assessment of SMARCA4 deficiency for the management of non-small cell lung cancer patients. This is imperative, as the contemporary shift on identifying biomarkers associated with tumor suppressor genes such as SMARCA4 are trending; hence, awareness of pathologists and clinicians is needed for the SMARCA4-dNSCLC entity with close follow-up on new management strategies to overcome the poor possibilities of survival in such patients.
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DOI：
10.1158/1078-0432.ccr-15-1468
发表时间：
2016-05-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Bell EH;Chakraborty AR;Mo X;Liu Z;Shilo K;Kirste S;Stegmaier P;McNulty M;Karachaliou N;Rosell R;Bepler G;Carbone DP;Chakravarti A
通讯作者：
Chakravarti A
影响因子：
3.5
作者：
Agaimy, Abbas;Fuchs, Florian;Haller, Florian
通讯作者：
Haller, Florian
影响因子：
2
作者：
Herpel, Esther;Rieker, Ralf J.;Agaimy, Abbas
通讯作者：
Agaimy, Abbas
影响因子：
5.3
作者：
Ilie, Marius;Beaulande, Melanie;Hofman, Paul
通讯作者：
Hofman, Paul
影响因子：
3.4
作者：
Chetty, Runjan;Serra, Stefano
通讯作者：
Serra, Stefano