多组学分析将皮脂腺癌与良性皮脂腺肿瘤区分开来，并深入了解皮脂腺癌发生的遗传进化。

Multiomics Profiling Distinguishes Sebaceous Carcinoma from Benign Sebaceous Neoplasms and Provides Insight into the Genetic Evolution of Sebaceous Carcinogenesis.

机构信息

Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia.

出版信息

Clin Cancer Res. 2024 Nov 1;30(21):4887-4899. doi: 10.1158/1078-0432.CCR-24-1327.

DOI:10.1158/1078-0432.CCR-24-1327

PMID:39287419

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11530307/

Abstract

PURPOSE

Sebaceous carcinoma is the third most common nonkeratinocyte skin cancer in the United States with 1,000 cases per year. The clinicopathologic features of sebaceous carcinoma and benign sebaceous neoplasms (adenomas, sebaceomas) can overlap, highlighting the need for molecular biomarkers to improve classification. This study describes the genomic and transcriptomic landscape of sebaceous neoplasms in order to understand tumor etiology and biomarkers relevant for diagnosis and treatment.

EXPERIMENTAL DESIGN

We performed whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS) of sebaceous neoplasms from six academic and two federal healthcare facilities in the United States diagnosed between January 1, 1999, and December 31, 2021.

RESULTS

We evaluated 98 sebaceous neoplasms: 64 tumors (32 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 25 carcinomas) had sufficient material for WGS, 96 tumors (42 adenomas, 11 sebaceomas, 8 atypical sebaceous neoplasms, 35 carcinomas) had sufficient material for WTS, and 62 tumors (31 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 24 carcinomas) had sufficient material for combined WGS and WTS. Overall, we found decreased cholesterol biosynthesis and increased TP53 mutations, copy number gains (chromosome 6, 8q, and/or 18), and tumor mutation burden-high (>10 mutations/MB) in carcinomas compared to adenomas. Although diminished compared to adenomas, most carcinomas still had higher cholesterol biosynthesis than nonmalignant skin. Multiomics profiling also supported a precancerous model of tumor evolution with sebaceomas and atypical sebaceous neoplasms being likely intermediate lesions.

CONCLUSIONS

The study findings highlight key diagnostic biomarkers for sebaceous carcinoma and suggest that immunotherapy and modulation of cholesterol biosynthesis could be effective treatment strategies.

摘要

目的

在美国，皮脂腺癌是第三大常见的非角质形成细胞皮肤癌，每年有 1000 例。皮脂腺癌和良性皮脂腺肿瘤（腺瘤、皮脂瘤）的临床病理特征可能重叠，这突出表明需要分子生物标志物来改善分类。本研究描述了皮脂腺肿瘤的基因组和转录组图谱，以了解肿瘤的病因和与诊断和治疗相关的生物标志物。

实验设计

我们对 1999 年 1 月 1 日至 2021 年 12 月 31 日期间在美国六家学术和两家联邦医疗机构诊断的皮脂腺肿瘤进行了全基因组测序（WGS）和全转录组测序（WTS）。

结果

我们评估了 98 例皮脂腺肿瘤：64 例肿瘤（32 例腺瘤、2 例皮脂瘤、5 例非典型皮脂腺肿瘤、25 例癌）有足够的材料进行 WGS，96 例肿瘤（42 例腺瘤、11 例皮脂瘤、8 例非典型皮脂腺肿瘤、35 例癌）有足够的材料进行 WTS，62 例肿瘤（31 例腺瘤、2 例皮脂瘤、5 例非典型皮脂腺肿瘤、24 例癌）有足够的材料进行 WGS 和 WTS 联合分析。总的来说，与腺瘤相比，我们在癌中发现胆固醇生物合成减少，TP53 突变、拷贝数增益（6 号染色体、8q 和/或 18 号染色体）和肿瘤突变负担高（>10 个突变/MB）增加。尽管与腺瘤相比有所减少，但大多数癌仍然比非恶性皮肤具有更高的胆固醇生物合成。多组学分析还支持肿瘤进化的癌前模型，皮脂瘤和非典型皮脂腺肿瘤可能是中间病变。