Common and distinct patterns of acquired uniparental disomy and homozygous deletions between lung squamous cell carcinomas and lung adenocarcinoma.
Common and distinct patterns of acquired uniparental disomy and homozygous deletions between lung squamous cell carcinomas and lung adenocarcinoma.
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DOI：
10.1016/j.neo.2023.100932
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发表时间：
2023-11
期刊：
影响因子：
4.8
通讯作者：
Amos, Christopher, I
中科院分区：
文献类型：
--
作者：
Tuna, Musaffe;Mills, Gordon B.;Amos, Christopher, I
关键词：
获得性单亲二体性（aUPD）是一种染色体改变，可导致现有畸变的纯合性。我们使用来自癌症基因组图谱SNP阵列的数据来鉴定肺腺癌（LUAD）和肺鳞状细胞癌（LUSC）中不同和共同的aUPD谱。此外，我们还检测了aUPD与纯合缺失（HMD）、总生存期（OS）和无复发生存期（RFS）的相关性。总体而言，我们发现LUSC的aUPD（q = 5.34E-09）显著高于LUAD。在LUSC（24.9%）和LUAD（19.7%）中，HMD的显著部分与aUPD相关。我们鉴定了节段性、全染色体臂和全染色体aUPD，其中全7 p臂aUPD仅限于LUSC，而全染色体3 aUPD仅在LUAD中观察到，全染色体21 aUPD在LUSC和LUAD中是共同的。在LUAD和LUSC中，在CDKN 2A/B区观察到最常见的aUPD和HMD。在LUAD中，CDKN 2A/B区aUPD和HMD与较短的OS（q < 0.021和q < 0.005）和RFS（q < 0.005和q < 0.005）相关，而杂合缺失与OS和RFS无关。相反，在CDKN 2A/B区的aUPD与LUSC中的存活率之间未发现关联。在LUAD中，CTLA表达在CDKN 2A/B区具有aUPD的样品中显著低于没有拷贝数和基于等位基因的变化的样品。在LUAD中，免疫浸润与CDKN 2A/B的aUPD或HMD、HLA I类区域的增益以及全染色体q臂或全染色体的aUPD相关，但在LUSC中不相关。LUSC和LUAD都具有共同和不同的aUPD区域模式，具有不同的发生频率和与结果的相关性。
Acquired uniparental disomy (aUPD) is a chromosomal alteration that can lead to homozygosity of existing aberrations. We used data from The Cancer Genome Atlas SNP-based arrays to identify distinct and common aUPD profiles in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Moreover, we tested relevance of aUPD for homozygous deletion (HMD), overall survival (OS), and recurrence-free survival (RFS). Overall, we found significantly higher aUPD (q = 5.34E-09) in LUSC than in LUAD. A significant portion of HMD was associated with aUPD in LUSC (24.9%) and LUAD (19.7%). We identified segmental, whole-chromosome arm and whole-chromosome aUPD, in which whole 7p arm aUPD was restricted to LUSC, while whole-chromosome 3 aUPD was observed only in LUAD, and whole-chromosome 21 aUPD was common to both LUSC and LUAD. The most frequent aUPD and HMD were observed at CDKN2A/B region in both LUAD and LUSC. In LUAD, aUPD and HMD at CDKN2A/B region were associated with shorter OS (q < 0.021 and q < 0.005), and RFS (q < 0.005 and q < 0.005), while heterozygous deletion was not associated with OS and RFS. In contrast, no association was found between aUPD at CDKN2A/B region and survival in LUSC. In LUAD, CTLA expression was significantly lower in samples with aUPD at CDKN2A/B regions than in samples without copy number and allele-based changes. Immune infiltration correlated with aUPD or HMD at CDKN2A/B, gain at HLA class I region, and aUPD at whole-chromosome q-arm or whole chromosome in LUAD, but not in LUSC. Both LUSC and LUAD have common and distinct patterns of aUPD regions with differing frequencies of occurrence and associations with outcome.
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影响因子：
64.8
作者：
Minocherhomji, Sheroy;Ying, Songmin;Hickson, Ian D.
通讯作者：
Hickson, Ian D.
影响因子：
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作者：
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DOI：
10.1002/ajmg.1320060207
发表时间：
1980-01-01
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
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作者：
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通讯作者：
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50.3
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影响因子：
14.8
作者：
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