The importance of codon context for understanding the Ig-like somatic hypermutation strand-biased patterns in TP53 mutations in breast cancer

Lindley, Robyn A.

doi:10.1016/j.cancergen.2013.05.016

Cited by 23 publications

(32 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The observed targeting preferences for the deaminases studied are in general agreement with the results of a previous study of TP53 gene mutations using pooled breast cancer mutation data [8]. However, an unexpected finding was an observed difference between the targeting preferences for motifs associated with AID and APOBEC3G deaminase activity.…”

Section: Discussionsupporting

confidence: 89%

See 1 more Smart Citation

Association between targeted somatic mutation (TSM) signatures and HGS‐OvCa progression

et al. 2016

Self Cite

View full text Add to dashboard Cite

Evidence already exists that the activation‐induced cytidine deaminase (AID/APOBEC) and the adenosine deaminase (ADAR) families of enzymes are implicated as powerful mutagens in oncogenic processes in many somatic tissues. Each deaminase is identified by the DNA or RNA nucleotide sequence (“motif”) surrounding the nucleotide targeted for deamination. The primary objective of this study is to develop an in silico approach to identify nucleotide sequence changes of the target motifs of key deaminases during oncogenesis. If successful, a secondary objective is to investigate if such changes are associated with disease progression indicators that include disease stage and progression‐free survival time. Using a discovery cohort of 194 high‐grade serous ovarian adenocarcinoma (HGS‐OvCa) exomes, the results confirm the ability of the novel in silico approach used to identify changes in the preferred target motifs for AID, APOBEC3G, APOBEC3B, and ADAR1 during oncogenesis. Using this approach, a set of new cancer‐progression associated signatures (C‐PASs) were identified. Furthermore, it was found that the C‐PAS identified can be used to differentiate between the cohort of patients that remained progression‐free for longer than 60 months, from those in which disease progressed within 60 months (sensitivity 95%, specificity 90%). The spectrum of outcomes observed here could provide a foundation for future clinical assessment of susceptibility variants in ovarian, and several other cancers as disease progresses. The ability of the in silico methodology used to identify changes in deaminase motifs during oncogenesis also suggests new links between immune system function and tumorigenesis.

show abstract

Section: Discussionsupporting

confidence: 89%

“…The mutation targeting preferences off motifs associated with ADAR deaminase activity are consistent with the previous study of TP53 gene mutations for pooled breast cancer data [8]. Both datasets reveal a dominant ADAR target preference for A-to-G transitions at MC2 sites.…”

Section: Discussionsupporting

confidence: 87%

Association between targeted somatic mutation (TSM) signatures and HGS‐OvCa progression

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, the mutagenic potential of APOBEC3G is not restricted to the viral genome, and cytosine deamination may also occur in human DNA. The APOBEC‐related pattern of mutations, characterized by TpC>T transitions, can be observed in numerous human cancers, including HNSCC, and they are commonly described in the TP53 gene . Interestingly, oncogenic pathogens such as HPV and Helicobacter pylori have been proved to cause APOBEC3G‐mediated mutations in oral and gastric epithelium .…”

Section: Discussionmentioning

confidence: 99%

Distinct pattern of TP53 mutations in human immunodeficiency virus–related head and neck squamous cell carcinoma

Gleber‐Netto

Zhao

Trivedi

et al. 2017

Cancer

View full text Add to dashboard Cite

BACKGROUND Human immunodeficiency virus–infected individuals (HIVIIs) have a higher incidence of head and neck squamous cell carcinoma (HNSCC), and clinical and histopathological differences have been observed in their tumors in comparison with those of HNSCC patients without a human immunodeficiency virus (HIV) infection. The reasons for these differences are not clear, and molecular differences between HIV‐related HNSCC and non–HIV‐related HNSCC may exist. This study compared the mutational patterns of HIV‐related HNSCC and non–HIV‐related HNSCC. METHODS The DNA of 20 samples of HIV‐related HNSCCs and 32 samples of non–HIV‐related HNSCCs was sequenced. DNA libraries covering exons of 18 genes frequently mutated in HNSCC (AJUBA, CASP8, CCND1, CDKN2A, EGFR, FAT1, FBXW7, HLA‐A, HRAS, KEAP1, NFE2L2, NOTCH1, NOTCH2, NSD1, PIK3CA, TGFBR2, TP53, and TP63) were prepared and sequenced on an Ion Personal Genome Machine sequencer. DNA sequencing data were analyzed with Ion Reporter software. The human papillomavirus (HPV) status of the tumor samples was assessed with in situ hybridization, the MassARRAY HPV multiplex polymerase chain reaction assay, and p16 immunostaining. Mutation calls were compared among the studied groups. RESULTS HIV‐related HNSCC revealed a distinct pattern of mutations in comparison with non–HIV‐related HNSCC. TP53 mutation frequencies were significantly lower in HIV‐related HNSCC. Mutations in HIV+ patients tended to be TpC>T nucleotide changes for all mutated genes but especially for TP53. CONCLUSIONS HNSCC in HIVIIs presents a distinct pattern of genetic mutations, particularly in the TP53 gene. HIV‐related HNSCC may have a distinct biology, and an effect of the HIV virus on the pathogenesis of these tumors should not be ruled out. Cancer 2018;124:84‐94. © 2017 American Cancer Society.

show abstract

“…Recent studies have identified APOBEC mutation patterns in TP53 in BC (Lindley 2013) and lung adenocarcinoma (Waters et al 2015). Although these studies are useful to better understand the sequence and codon context of mutation formation in TP53, the amount of etiological information they reveal is limited compared with multigene studies using NGS.…”

Section: Mutation Patterns As Signatures Of Mutagenic Processesmentioning

confidence: 99%

SomaticTP53Mutations in the Era of Genome Sequencing

Hainaut

Pfeifer

2016

Cold Spring Harb Perspect Med

198

137

View full text Add to dashboard Cite

Amid the complexity of genetic alterations in human cancer, TP53 mutation appears as an almost invariant component, representing by far the most frequent genetic alteration overall. Compared with previous targeted sequencing studies, recent integrated genomics studies offer a less biased view of TP53 mutation patterns, revealing that .20% of mutations occur outside the DNA-binding domain. Among the 12 mutations representing each at least 1% of all mutations, five occur at residues directly involved in specific DNA binding, four affect the tertiary fold of the DNA-binding domain, and three are nonsense mutations, two of them in the carboxyl terminus. Significant mutations also occur in introns, affecting alternative splicing events or generating rearrangements (e.g., in intron 1 in sporadic osteosarcoma). In aggressive cancers, mutation is so common that it may not have prognostic value (all these cancers have impaired p53 function caused by mutation or by other mechanisms). In several other cancers, however, mutation makes a clear difference for prognostication, as, for example, in HER2-enriched breast cancers and in lung adenocarcinoma with EGFR mutations. Thus, the clinical significance of TP53 mutation is dependent on tumor subtype and context. Understanding the clinical impact of mutation will require integrating mutationspecific information (type, frequency, and predicted impact) with data on haplotypes and on loss of heterozygosity.

show abstract

The importance of codon context for understanding the Ig-like somatic hypermutation strand-biased patterns in TP53 mutations in breast cancer

Cited by 23 publications

References 11 publications

Association between targeted somatic mutation (TSM) signatures and HGS‐OvCa progression

Association between targeted somatic mutation (TSM) signatures and HGS‐OvCa progression

Distinct pattern of TP53 mutations in human immunodeficiency virus–related head and neck squamous cell carcinoma

SomaticTP53Mutations in the Era of Genome Sequencing

Contact Info

Product

Resources

About