The Genomic Atlas of Dermatological Tumours (DERMATLAS)

皮肤肿瘤基因组图谱 (DERMATLAS)

• 批准号: MR/V000292/1
• 负责人: David Adams
• 金额: $ 208.29万
• 依托单位: Wellcome Sanger Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV000292%2F1
• 关键词: Genomic; Atlas; Dermatological; Tumours; DERMATLAS

There is a misconception that skin cancers, Europe's most common type of tumour, are treatable with surgery and are thus not a research priority. The reality is that while many patients can be adequately managed with surgical intervention, surgery is often disfiguring and can be associated with significant morbidity. Notably, many skin tumour types such as cutaneous angiosarcoma, Merkel cell carcinoma and some sarcomatoid/spindle cell carcinomas are associated with an extremely poor prognosis. Importantly, in the clinic the classification of skin tumour types can be extremely challenging, particularly determining benign from malignant lesions with the exact diagnosis having profound implications for patient outcome and management. Unlike more common cancers, the genomes of most skin malignancies have not been studied in detail and treatment options in advanced disease are limited. In terms of the etiology of skin cancers, another misnomer is that most skin cancers are UV-associated. While this is certainly the case for some types of melanoma, BCCs and squamous cell carcinoma, the cause of most other types is unknown. Some tumours such as Merkel cell carcinoma are associated with viruses (Merkel cell polyomavirus) while HPV has been suggested to play a role in other entities but the role of viruses or other exposures has been poorly explored. In this project we plan to use genetic analysis to identify how and why a wide range of skin tumours develop, with the possible implications for this work being enhanced patient management, better diagnosis and an improved understanding of the basic biology of skin.

人们有一种误解，认为皮肤癌是欧洲最常见的肿瘤类型，可以通过手术治疗，因此不是研究的重点。现实情况是，虽然许多患者可以通过手术干预得到充分治疗，但手术往往会毁容，并可能导致严重的发病率。值得注意的是，许多皮肤肿瘤类型，例如皮肤血管肉瘤、默克尔细胞癌和一些肉瘤样/梭形细胞癌，与极差的预后相关。重要的是，在临床上，皮肤肿瘤类型的分类可能极具挑战性，特别是确定良性和恶性病变，准确的诊断对患者的治疗结果和治疗具有深远的影响。与更常见的癌症不同，大多数皮肤恶性肿瘤的基因组尚未得到详细研究，晚期疾病的治疗选择也很有限。就皮肤癌的病因学而言，另一个错误的说法是大多数皮肤癌与紫外线有关。虽然某些类型的黑色素瘤、基底细胞癌和鳞状细胞癌确实属于这种情况，但大多数其他类型的原因尚不清楚。默克尔细胞癌等一些肿瘤与病毒（默克尔细胞多瘤病毒）有关，而 HPV 已被认为在其他实体中发挥作用，但病毒或其他暴露的作用尚未得到充分探索。在这个项目中，我们计划使用遗传分析来确定各种皮肤肿瘤如何以及为何发生，这项工作的可能影响是加强患者管理、更好的诊断和更好地了解皮肤的基本生物学。

项目成果

Analysis of CRISPR-Cas9 screens identifies genetic dependencies in melanoma.

• DOI: 10.1111/pcmr.12919
• 发表时间: 2021-01
• 期刊: Pigment cell & melanoma research
• 影响因子: 4.3
• 作者: Christodoulou E;Rashid M;Pacini C;Droop A;Robertson H;Groningen TV;Teunisse AFAS;Iorio F;Jochemsen AG;Adams DJ;Doorn RV
• 通讯作者: Doorn RV

Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation.

• DOI: 10.1016/j.devcel.2021.08.018
• 发表时间: 2021-10-25
• 期刊: Developmental cell
• 影响因子: 11.8
• 作者: Campbell NR;Rao A;Hunter MV;Sznurkowska MK;Briker L;Zhang M;Baron M;Heilmann S;Deforet M;Kenny C;Ferretti LP;Huang TH;Perlee S;Garg M;Nsengimana J;Saini M;Montal E;Tagore M;Newton-Bishop J;Middleton MR;Corrie P;Adams DJ;Rabbie R;Aceto N;Levesque MP;Cornell RA;Yanai I;Xavier JB;White RM
• 通讯作者: White RM

Variant Library Annotation Tool (VaLiAnT): an oligonucleotide library design and annotation tool for saturation genome editing and other deep mutational scanning experiments.

• DOI: 10.1093/bioinformatics/btab776
• 发表时间: 2022-01-27
• 期刊: Bioinformatics (Oxford, England)
• 作者: Barbon L;Offord V;Radford EJ;Butler AP;Gerety SS;Adams DJ;Tan HK;Waters AJ
• 通讯作者: Waters AJ

Editorial overview: The most difficult of years in cancer research.

编辑概述：癌症研究中最困难的几年。

• DOI: 10.1016/j.gde.2021.02.001
• 发表时间: 2021
• 期刊: Current opinion in genetics & development
• 影响因子: 4
• 作者: Adams DJ

Ethanol-induced formation of colorectal tumours and precursors in a mouse model of Lynch syndrome.

• DOI: 10.1002/path.5796
• 发表时间: 2021-12
• 期刊: The Journal of pathology