Atypical UV Photoproducts Induce Non-canonical Mutation Classes Associated with Driver Mutations in Melanoma.
Atypical UV Photoproducts Induce Non-canonical Mutation Classes Associated with Driver Mutations in Melanoma.
复制标题
非典型紫外光产物诱导黑色素瘤中与驱动突变相关的非典型突变类别。
DOI：
10.1016/j.celrep.2020.108401
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发表时间：
2020-11-17
期刊：
影响因子：
8.8
通讯作者：
Wyrick JJ
中科院分区：
文献类型：
--
作者：
Laughery MF;Brown AJ;Bohm KA;Sivapragasam S;Morris HS;Tchmola M;Washington AD;Mitchell D;Mather S;Malc EP;Mieczkowski PA;Roberts SA;Wyrick JJ
皮肤癌和其他紫外线（UV）暴露细胞中的体细胞突变以二嘧啶序列的C>T和CC>TT取代为代表;然而，黑色素瘤中的许多致癌“驱动”突变不符合这种UV特征。在这里，我们使用基因组测序来表征反复用紫外线照射的酵母中的突变。对约50，000个UV诱导的突变的分析揭示了丰富的非典型突变，包括T>C、T>A和AC>TT取代。这些突变显示转录的不对称性，这是由核苷酸切除修复（NER）调制，表明它们是由UV光产物。使用称为UV DNA核酸内切酶测序（UVDE-seq）的测序方法，我们证实了一种非典型的胸腺嘧啶-腺嘌呤光产物的存在，可能是UV诱导的T>A取代的原因。皮肤癌中也存在类似的非典型突变，它们也显示出转录不对称性和对NER的依赖性。这些包括多个驱动突变，最突出的是复发性BRAF V600 E和V600 K置换，表明罕见的非典型UV光产物引起的突变可能在黑色素瘤发生中起作用。UV诱变已经得到了很好的研究，但黑色素瘤中的许多驱动突变不符合规范的UV特征。使用全基因组测序，Laughery等人表明，紫外线诱导的突变谱比预期的更广。非典型的紫外线突变可能是由非典型的光产物引起的，这可能有助于黑色素瘤的发生。
Somatic mutations in skin cancers and other ultraviolet (UV)-exposed cells are typified by C>T and CC>TT substitutions at dipyrimidine sequences; however, many oncogenic “driver” mutations in melanoma do not fit this UV signature. Here, we use genome sequencing to characterize mutations in yeast repeatedly irradiated with UV light. Analysis of ~50,000 UV-induced mutations reveals abundant non-canonical mutations, including T>C, T>A, and AC>TT substitutions. These mutations display transcriptional asymmetry that is modulated by nucleotide excision repair (NER), indicating that they are caused by UV photoproducts. Using a sequencing method called UV DNA endonuclease sequencing (UVDE-seq), we confirm the existence of an atypical thymine-adenine photoproduct likely responsible for UV-induced T>A substitutions. Similar non-canonical mutations are present in skin cancers, which also display transcriptional asymmetry and dependence on NER. These include multiple driver mutations, most prominently the recurrent BRAF V600E and V600K substitutions, suggesting that mutations arising from rare, atypical UV photoproducts may play a role in melanomagenesis. UV mutagenesis has been well studied, but many driver mutations in melanoma do not fit the canonical UV signature. Using whole-genome sequencing, Laughery et al. show that UV induces a broader spectrum of mutations than anticipated. Non-canonical UV mutations are likely caused by atypical photoproducts, which may contribute to melanomagenesis.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
64.5
作者：
Haradhvala NJ;Polak P;Stojanov P;Covington KR;Shinbrot E;Hess JM;Rheinbay E;Kim J;Maruvka YE;Braunstein LZ;Kamburov A;Hanawalt PC;Wheeler DA;Koren A;Lawrence MS;Getz G
通讯作者：
Getz G
影响因子：
56.9
作者：
BOSE, SN;DAVIES, RJH;MCCLOSKEY, JA
通讯作者：
MCCLOSKEY, JA
DOI：
10.1073/pnas.70.8.2281
发表时间：
1973-01-01
影响因子：
11.1
作者：
AMES, BN;DURSTON, WE;LEE, FD
通讯作者：
LEE, FD