基因组分析定义了肺癌类肺癌的独特的胰腺和神经元亚型
Clara Domingo-Sabugo1, Saffron Ag Willis-Owen1, Amit Mandal1
1National Heart and Lung Institute, Imperial College London, London, UK.
The Journal of pathology
|September 27, 2024
概括
这项研究揭示了基于转录组和表观组资料的两个不同的肺癌类型 (L-CDs),L-CD-PanC和L-CD-NeU. 这些亚型表现出独特的分子,临床和免疫特征,为向肺癌治疗提供了新的途径.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 肺癌 (L-CDs) 是一种罕见的神经内分泌瘤,具有不完美的组织学分类.
- 非典型的癌类药物 (ACs) 与较差的生存率有关,这突出了改善诊断和治疗策略的需要.
- 分子标记物对于理解L-CD异质性越来越重要.
研究的目的:
- 调查L-CDs的全球转录组和表观组资料.
- 识别L-CDs的不同分子亚型及其潜在的遗传和表观遗传变化.
- 探索L-CD亚型之间的病原和免疫微环境的潜在差异.
主要方法:
- 整体外体序列 (WES) 和15个L-CDs的单核酸多态 (SNP) 基因定型.
- 转录组集群用于识别L-CD亚型.
- 对DNA甲基化,突变特征和免疫细胞透的分析.
主要成果:
- 确定了两个不同的L-CD亚型:L-CD-PanC和L-CD-NeU.
- L-CD-PanC瘤显示胰腺/代谢基因上调,β细胞/胰岛素分泌基因低甲基化,以及特定的突变特征.
- L-CD-NeU瘤表现出神经元标记物上调,状细胞形态,更高的突变负载和明显的突变特征,可能与环境暴露有关.
结论:
- 鉴定L-CD-PanC和L-CD-NeU亚型为L-CD异质性提供了分子基础.
- 亚型之间明显的表观遗传和非编码差异为生物标志物开发提供了机会.
- 这些发现为基于分子分类的L-CD的向治疗策略铺平了道路.
相关概念视频
lncRNA - Long Non-coding RNAs
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...
Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Cancer-Critical Genes I: Proto-oncogenes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
Cancer-Critical Genes I: Proto-oncogenes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...


