在广泛的皮肤黑色素细胞瘤中发现的基因揭示了多种马赛克原因
Nicole Knöpfel1,2,3, Sara Barberan-Martin1,2, Satyamaanasa Polubothu2,3
1Mosaicism and Precision Medicine Lab, The Francis Crick Institute, London, UK.
The British journal of dermatology
|November 27, 2025
概括
广泛的皮肤黑色细胞瘤 (EDM) 经常被误诊. 基因检测发现了新的致病基因,扩大了对这种疾病及其相关风险的理解.
科学领域:
- 遗传学 是一个遗传学.
- 皮肤病学 皮肤病学
- 眼科医生 眼科 眼科
背景情况:
- 广泛的和/或非典型的皮肤黑色细胞瘤 (EDM) 呈现为异常的皮肤颜色.
- 由于与良性疾病的重叠,EDM的诊断不足,并且经常被误诊为先天性黑色细胞瘤.
- EDM的遗传基础在很大程度上是未知的,只有GNAQ变种在少数情况下被确定.
研究的目的:
- 调查广泛和/或非典型皮肤黑色素细胞病 (EDM) 的遗传原因.
- 在EDM患者中确定相关的临床异常.
- 为了区分EDM与常见的短暂皮肤黑色素细胞症.
主要方法:
- 47名患有EDM的患者的表型评估.
- 针对受影响皮肤的深度下一代测序.
- 在精选患者中进行眼科检查和中枢神经系统MRI.
主要成果:
- 眼科参与发生在40%的患者身上,无论皮肤位置如何.
- 在5名扫描患者中,有2名观察到缺血性心脏病发作.
- 在HRAS,ACTB,PIK3CA和GNA11的马赛克变异被确定为EDM的新遗传原因,以及其他GNAQ病例.
结论:
- 区分EDM和良性疾病至关重要;即使没有周期性参与,也建议进行眼科查.
- 在EDM和中枢神经系统梗塞之间的关联需要进一步调查,建议临床神经学评估.
- 这些发现扩大了EDM的遗传谱,可能有助于未来的黑色素瘤风险分层和遗传咨询.
相关概念视频
Skin Cancer
5.7K
Skin cancer is a type of cancer that occurs when there is an abnormal growth of skin cells, usually triggered by damage to the DNA within the skin cells. It is primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Skin cancer is the most common type of cancer worldwide, and its incidence continues to rise.
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
5.7K
Pigmentation
4.1K
The color of the skin is influenced by a number of pigments, including melanin, carotene, and hemoglobin. Recall that melanin is produced by cells called melanocytes, which are found scattered throughout the stratum basale of the epidermis. The melanin is transferred to the keratinocytes via melanosomes.
Melanin occurs in two primary forms: eumelanin that provides black and brown pigment and pheomelanin that provides red color. Dark-skinned individuals produce more melanin than those with pale...
Melanin occurs in two primary forms: eumelanin that provides black and brown pigment and pheomelanin that provides red color. Dark-skinned individuals produce more melanin than those with pale...
4.1K
Cancers Originate from Somatic Mutations in a Single Cell
14.5K
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...
14.5K
Induced Pluripotent Stem Cells
5.3K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
5.3K
Nucleotide Excision Repair
4.9K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
4.9K
Pleiotropy
43.1K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
43.1K


