Testing tumors from different anatomic sites for clonal relatedness using somatic mutation data.
Testing tumors from different anatomic sites for clonal relatedness using somatic mutation data.
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DOI：
10.1111/biom.13256
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发表时间：
2021-03
期刊：
影响因子：
1.9
通讯作者：
Begg CB
中科院分区：
文献类型：
--
作者：
Ostrovnaya I;Mauguen A;Seshan VE;Begg CB
癌症病理学家的常见任务是确定在患有癌症的患者中，与原发肿瘤不同的解剖部位中的新肿瘤是独立发生的癌症还是转移。随着肿瘤的突变谱在常规临床实践中变得更加普遍，通过比较肿瘤的突变谱以确定它们是否足够相似以得出肿瘤是克隆相关的结论，即一个是另一个的转移，可以大大增强该诊断任务。我们在这里提出了一个似然比检验克隆相关性在这种情况下，并提供证据证明其有效性。该测试是不寻常的，因为有两个可能的替代假设，代表两个解剖部位，从该单一克隆细胞可能最初出现。尽管克隆相关性的证据在很大程度上是由两种肿瘤中存在精确的突变匹配提供的，但我们表明，即使没有观察到匹配，也可以观察到测试具有统计学显著性的数据。当其中一个肿瘤的突变谱与另一个肿瘤的解剖部位紧密对齐时，可能会发生这种情况，间接表明肿瘤起源于另一个部位。我们展示这种现象的例子，并建议在实践中解释这些测试的结果的策略。
A common task for the cancer pathologist is to determine, in a patient suffering from cancer, whether a new tumor in a distinct anatomic site from the primary is an independent occurrence of cancer or a metastasis. As mutational profiling of tumors becomes more widespread in routine clinical practice this diagnostic task can be greatly enhanced by comparing mutational profiles of the tumors to determine if they are sufficiently similar to conclude that the tumors are clonally related, i.e. one is a metastasis of the other. We present here a likelihood ratio test for clonal relatedness in this setting and provide evidence of its validity. The test is unusual in that there are two possible alternative hypotheses, representing the two anatomic sites from which the single clonal cell could have initially emerged. Even though evidence for clonal relatedness is largely provided by the presence of exact mutational matches in the two tumors, we show that it is possible to observe data where the test is statistically significant even when no matches are observed. This can occur when the mutational profile of one of the tumors is closely aligned with the anatomic site of the other tumor, suggesting indirectly that the tumor originated in that other site. We exhibit examples of this phenomenon and recommend a strategy for interpreting the results of these tests in practice.
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影响因子：
16.6
作者：
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影响因子：
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作者：
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影响因子：
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作者：
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