光学基因组图谱揭示了与 HBOC 相关的乳腺癌中结构变异及其临床意义的全景。
Optical Genome Mapping Reveals the Landscape of Structural Variations and Their Clinical Significance in HBOC-Related Breast Cancer.
机构信息
Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060 Tianjin, China.
Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Cancer Immunology and Biotherapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, 300060 Tianjin, China.
出版信息
Front Biosci (Landmark Ed). 2024 Jan 9;29(1):2. doi: 10.31083/j.fbl2901002.
BACKGROUND
Structural variations (SVs) are common genetic alterations in the human genome. However, the profile and clinical relevance of SVs in patients with hereditary breast and ovarian cancer (HBOC) syndrome (germline mutations) remains to be fully elucidated.
METHODS
Twenty HBOC-related cancer samples (5 breast and 15 ovarian cancers) were studied by optical genome mapping (OGM) and next-generation sequencing (NGS) assays.
RESULTS
The SV landscape in the 5 HBOC-related breast cancer samples was comprehensively investigated to determine the impact of intratumor SV heterogeneity on clinicopathological features and on the pattern of genetic alteration. SVs and copy number variations (CNVs) were common genetic events in HBOC-related breast cancer, with a median of 212 SVs and 107 CNVs per sample. The most frequently detected type of SV was insertion, followed by deletion. The 5 HBOC-related breast cancer samples were divided into SVhigh and SVlow groups according to the intratumor heterogeneity of SVs. SVhigh tumors were associated with higher Ki-67 expression, higher homologous recombination deficiency (HRD) scores, more mutated genes, and altered signaling pathways. Moreover, 60% of the HBOC-related breast cancer samples displayed chromothripsis, and 8 novel gene fusion events were identified by OGM and validated by transcriptome data.
CONCLUSIONS
These findings suggest that OGM is a promising tool for the detection of SVs and CNVs in HBOC-related breast cancer. Furthermore, OGM can efficiently characterize chromothripsis events and novel gene fusions. SVhigh HBOC-related breast cancers were associated with unfavorable clinicopathological features. SVs may therefore have predictive and therapeutic significance for HBOC-related breast cancers in the clinic.
背景
结构变异（SVs）是人类基因组中常见的遗传改变。然而，遗传性乳腺癌和卵巢癌（HBOC）综合征（种系突变）患者中 SV 的特征和临床相关性仍有待充分阐明。
方法
通过光学基因组图谱（OGM）和下一代测序（NGS）检测，对 20 例 HBOC 相关癌症样本（5 例乳腺癌和 15 例卵巢癌）进行研究。
结果
全面研究了 5 例 HBOC 相关乳腺癌样本中的 SV 景观，以确定肿瘤内 SV 异质性对临床病理特征和遗传改变模式的影响。SVs 和拷贝数变异（CNVs）是 HBOC 相关乳腺癌中的常见遗传事件，每个样本中存在中位数为 212 个 SVs 和 107 个 CNVs。最常见的 SV 类型是插入，其次是缺失。根据 SV 肿瘤内异质性，将 5 例 HBOC 相关乳腺癌样本分为 SVhigh 和 SVlow 组。SVhigh 肿瘤与更高的 Ki-67 表达、更高的同源重组缺陷（HRD）评分、更多的突变基因和改变的信号通路相关。此外，60%的 HBOC 相关乳腺癌样本显示染色体重排，通过 OGM 鉴定并通过转录组数据验证了 8 个新的基因融合事件。
结论
这些发现表明，OGM 是检测 HBOC 相关乳腺癌中 SVs 和 CNVs 的有前途的工具。此外，OGM 可以有效地描述染色体重排事件和新的基因融合。SVhigh HBOC 相关乳腺癌与不良的临床病理特征相关。因此，SVs 可能对 HBOC 相关乳腺癌的临床具有预测和治疗意义。
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