期刊
PIGMENT CELL & MELANOMA RESEARCH
卷 33, 期 3, 页码 480-489出版社
WILEY
DOI: 10.1111/pcmr.12851
关键词
chronic sun damage; heterogeneity; in situ; invasive; melanoma
资金
- National Health Services
- Fru Berta Kamprads Stiftelse
- Mats Paulsson Foundation
- Hudfonden
- Horizon 2020 Framework Programme [247634]
- Crafoordska Stiftelsen
- Stefan Paulsson Foundation
- LMK foundation
- Swedish Research Council
- Swedish Cancer Society
- governmental funding for healthcare research (ALF)
- Gunnar Nilssons Cancerstiftelse
- Gorthon foundation
Chronic sun-damaged (CSD) melanoma represents 10%-20% of cutaneous melanomas and is characterized by infrequent BRAF V600E mutations and high mutational load. However, the order of genetic events or the extent of intra-tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. Ultra-deep targeted sequencing of 40 cancer-associated genes was performed in 72 in situ or invasive CMM, including 23 CSDhigh cases. In addition, we performed whole exome and RNA sequencing on multiple regions of primary tumor and multiple in-transit metastases from one CSDhigh melanoma patient. We found no significant difference in mutation frequency in melanoma-related genes or in mutational load between in situ and invasive CSDhigh lesions, while this difference was observed in CSDlow lesions. In addition, increased frequency of BRAF V600K, NF1, and TP53 mutations (p < .01, Fisher's exact test) was found in CSDhigh melanomas. Sequencing of multiple specimens from one CSDhigh patient revealed strikingly limited ITH with >95% shared mutations. Our results provide evidence that CSDhigh and CSDlow melanomas are distinct molecular entities that progress via different genetic routes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据