Algoma District Cancer Program, Sault Area Hospital, Sault Ste. Marie, Ontario, Canada.
Section of Internal Medicine, Division of Clinical Sciences, Northern Ontario School of Medicine, Sudbury, Ontario, Canada.
Cancer Invest. 2021 Jan;39(1):25-38. doi: 10.1080/07357907.2020.1863418. Epub 2020 Dec 22.
Chromosomal instability (CIN) is a defining characteristic of cancer and is part of the genetic instability of cancer. CIN results in both numeric alterations of chromosomes also called aneuploidy and in gains or losses of parts of chromosome arms but both usually coexist. The frequency and distribution of CIN varies between cancer types and even in the same cancer and breast cancer is no exception. Its presence may provide prognostic and therapeutic opportunities.
CIN as measured with a score named Aneuploidy Score (AS) derived from single nucleotide polymorphism array studies was examined using the breast cancer study from the Cancer Genome Atlas (TCGA). Correlations of the AS with sub-types of breast cancer and with the tumor mutation burden (TMB) were examined. Specific copy number alterations contributing to the AS and their associations with sub-types were also investigated.
Most breast cancers (about 75% in the series) present some degree of CIN, having an AS of above 5. The remaining 25% have AS of 5 or below. Luminal A sub-type is over-represented in cancers with low AS while the reverse is true for cancers with high AS where the percentage of the three other sub-types, luminal B, Her2 positive and basal is higher. Common gains of chromosomal arms are observed in 1q, 8q and 16p and losses are commonly present in 16q, 17p and 8p but with variability among sub-types. A chromosome loss characterizing basal cancers is observed at 5q. No association of AS with TMB is observed in breast cancer. AS was not predictive for survival outcomes in the entire cohort of breast cancers, but PFS was significant worse in luminal B cancers with high AS.
The copy number alterations landscape of breast cancer reveals specific abnormalities in each sub-type and may help further characterize these sub-types in order to refine classification of these cancers and promote prognostic and therapeutic advancements in the clinic.
染色体不稳定（CIN）是癌症的一个定义特征，也是癌症遗传不稳定性的一部分。CIN 导致染色体的数量改变，也称为非整倍体，以及染色体臂的部分增益或损失，但两者通常同时存在。CIN 的频率和分布在不同的癌症类型之间甚至在同一癌症中都有所不同，乳腺癌也不例外。它的存在可能提供预后和治疗机会。
使用从单核苷酸多态性阵列研究中得出的名为非整倍体评分（AS）的评分来检查癌症基因组图谱（TCGA）中的乳腺癌研究。检查 AS 与乳腺癌亚型和肿瘤突变负担（TMB）的相关性。还研究了导致 AS 的特定拷贝数改变及其与亚型的关联。
大多数乳腺癌（该系列中约 75%）存在某种程度的 CIN，其 AS 高于 5。其余 25%的 AS 为 5 或更低。低 AS 的癌症中，Luminal A 亚型过度表达，而高 AS 的癌症则相反，其中三种其他亚型（Luminal B、Her2 阳性和基底）的比例更高。常见的染色体臂增益发生在 1q、8q 和 16p，而常见的缺失发生在 16q、17p 和 8p，但在亚型之间存在差异。基底癌中存在一个特征性的 5q 染色体缺失。在乳腺癌中未观察到 AS 与 TMB 的关联。AS 对整个乳腺癌队列的生存结果没有预测性，但在高 AS 的 Luminal B 癌症中，无进展生存期显著更差。
乳腺癌的拷贝数改变图谱揭示了每个亚型的特定异常，这可能有助于进一步表征这些亚型，以完善这些癌症的分类，并促进临床预后和治疗的进展。
