Genomic characterization of small cell carcinomas of the uterine cervix.
Genomic characterization of small cell carcinomas of the uterine cervix.
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DOI：
10.1002/1878-0261.12962
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发表时间：
2022-03
影响因子：
6.6
通讯作者：
Weigelt B
中科院分区：
文献类型：
--
作者：
Schultheis AM;de Bruijn I;Selenica P;Macedo GS;da Silva EM;Piscuoglio S;Jungbluth AA;Park KJ;Klimstra DS;Wardelmann E;Hartmann W;Gerharz CD;von Petersdorff M;Buettner R;Reis-Filho JS;Weigelt B
宫颈小细胞癌（SCC）是一种罕见的侵袭性神经内分泌癌，其组织学与小细胞肺癌（SCLC）相似，生存率低。在这里，我们试图定义宫颈SCCs的遗传基础，并使用公开数据将其突变谱与人乳头瘤病毒（HPV）阳性的头颈部鳞状细胞癌、HPV阳性的宫颈癌和SCCs进行比较。使用全外显子组和靶向大规模平行测序的组合，我们发现9例宫颈SCCs， HPV18阳性（n = 8）或HPV16阳性（n = 1），具有低突变负担，拷贝数改变很少，除TP53外，2例无复发突变基因。大多数突变可能是乘客错义突变，只有少数影响先前描述的癌症相关基因。通过RNA测序，我们确定了两个子宫颈SCCs的18q12.3和8p22上可能的病毒整合位点。宫颈鳞状细胞癌的总体非沉默突变率明显低于宫颈鳞状细胞癌、HPV驱动的宫颈腺癌和鳞状细胞癌，或HPV阳性的头颈部鳞状细胞癌。与据报道几乎普遍存在TP53和RB1突变和显性烟草烟雾相关特征的SCCs不同，宫颈SCCs很少存在影响这些基因的突变（2/ 9,22% TP53; 0% RB1），并表现出显性衰老（67%）或APOBEC突变特征（17%），类似于HPV驱动的癌症，包括宫颈腺癌和鳞状细胞癌以及头颈部鳞状细胞癌。总之，与以TP53和RB1高复发性改变为特征的SCCs相反，宫颈SCCs对HPV呈阳性，导致抑制因子p53和RB失活，表明这些SCCs是趋同表型。宫颈小细胞癌（SCC）是一种罕见的侵袭性神经内分泌癌。在这里，我们发现宫颈SCCs主要是HPV18阳性。使用全外显子组和/或靶向大规模平行测序，我们发现子宫颈SCCs具有低突变负担，很少携带TP53和缺乏RB1突变，显示主要显性衰老突变特征，并且缺乏复发扩增/纯合缺失。
Small cell carcinoma (SCC) of the uterine cervix is a rare and aggressive form of neuroendocrine carcinoma, which resembles small cell lung cancer (SCLC) in its histology and poor survival rate. Here, we sought to define the genetic underpinning of SCCs of the uterine cervix and compare their mutational profiles with those of human papillomavirus (HPV)‐positive head and neck squamous cell carcinomas, HPV‐positive cervical carcinomas, and SCLCs using publicly available data. Using a combination of whole‐exome and targeted massively parallel sequencing, we found that the nine uterine cervix SCCs, which were HPV18‐positive (n = 8) or HPV16‐positive (n = 1), harbored a low mutation burden, few copy number alterations, and other than TP53 in two cases no recurrently mutated genes. The majority of mutations were likely passenger missense mutations, and only few affected previously described cancer‐related genes. Using RNA‐sequencing, we identified putative viral integration sites on 18q12.3 and on 8p22 in two SCCs of the uterine cervix. The overall nonsilent mutation rate of uterine cervix SCCs was significantly lower than that of SCLCs, HPV‐driven cervical adeno‐ and squamous cell carcinomas, or HPV‐positive head and neck squamous cell carcinomas. Unlike SCLCs, which are reported to harbor almost universal TP53 and RB1 mutations and a dominant tobacco smoke‐related signature 4, uterine cervix SCCs rarely harbored mutations affecting these genes (2/9, 22% TP53; 0% RB1) and displayed a dominant aging (67%) or APOBEC mutational signature (17%), akin to HPV‐driven cancers, including cervical adeno‐ and squamous cell carcinomas and head and neck squamous cell carcinomas. Taken together, in contrast to SCLCs, which are characterized by highly recurrent TP53 and RB1 alterations, uterine cervix SCCs were positive for HPV leading to inactivation of the suppressors p53 and RB, suggesting that these SCCs are convergent phenotypes. Small cell carcinoma (SCC) of the uterine cervix is a rare and aggressive neuroendocrine carcinoma. Here, we show that uterine cervix SCCs are primarily HPV18‐positive. Using whole‐exome and/or targeted massively parallel sequencing, we found that uterine cervix SCCs have a low mutation burden, rarely harbor TP53 and lack RB1 mutations, display primarily dominant aging mutational signatures, and lack recurrent amplifications/homozygous deletions.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
64.8
作者：
通讯作者：
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DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
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影响因子：
28.2
作者：
Chang MT;Bhattarai TS;Schram AM;Bielski CM;Donoghue MTA;Jonsson P;Chakravarty D;Phillips S;Kandoth C;Penson A;Gorelick A;Shamu T;Patel S;Harris C;Gao J;Sumer SO;Kundra R;Razavi P;Li BT;Reales DN;Socci ND;Jayakumaran G;Zehir A;Benayed R;Arcila ME;Chandarlapaty S;Ladanyi M;Schultz N;Baselga J;Berger MF;Rosen N;Solit DB;Hyman DM;Taylor BS
通讯作者：
Taylor BS
影响因子：
46.9
作者：
通讯作者：
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