ERα-related chromothripsis enhances concordant gene transcription on chromosome 17q11.1-q24.1 in luminal breast cancer

Lin, Chun-Lin; Tan, Xueying; Chen, Chun-Liang; Kusi, Meena; Hung, Chia-Nung; Hsu, Ya-Ting; Wang, Chiou‐Miin; Kirma, Nameer B.; Lin, Ching-Hung; Lathrop, Kate; Elledge, Richard M.; Kaklamani, Virginia; Mitsuya, Kohzoh; Huang, Tim H.M.

doi:10.1186/s12920-020-0729-7

Cited by 13 publications

(7 citation statements)

References 74 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nuclear hormone receptors, exemplified by AR (androgen receptor) and ESR1 (oestrogen receptor 1) in both our datasets, are recognized mediators of long-range interactions ( 71 , 109 ) and epigenetic remodelling ( 110 ). Liganded ERα interplays with cohesin to instigate chromatin looping ( 111 , 112 ) and chromothripsis in breast cancer cell lines ( 113 ). Analogously, liganded AR expedites chromosomal translocations by nucleating distant loci that are ligated by NHEJ following targeted nuclease activity ( 109 ).…”

Section: Discussionmentioning

confidence: 99%

Tracking telomere fusions through crisis reveals conflict between DNA transcription and the DNA damage response

et al. 2021

View full text Add to dashboard Cite

Identifying attributes that distinguish pre-malignant from senescent cells provides opportunities for targeted disease eradication and revival of anti-tumour immunity. We modelled a telomere-driven crisis in four human fibroblast lines, sampling at multiple time points to delineate genomic rearrangements and transcriptome developments that characterize the transition from dynamic proliferation into replicative crisis. Progression through crisis was associated with abundant intra-chromosomal telomere fusions with increasing asymmetry and reduced microhomology usage, suggesting shifts in DNA repair capacity. Eroded telomeres also fused with genomic loci actively engaged in transcription, with particular enrichment in long genes. Both gross copy number alterations and transcriptional responses to crisis likely underpin the elevated frequencies of telomere fusion with chromosomes 9, 16, 17, 19 and most exceptionally, chromosome 12. Juxtaposition of crisis-regulated genes with loci undergoing de novo recombination exposes the collusive contributions of cellular stress responses to the evolving cancer genome.

show abstract

Section: Discussionmentioning

confidence: 99%

Tracking telomere fusions through crisis reveals conflict between DNA transcription and the DNA damage response

et al. 2021

View full text Add to dashboard Cite

show abstract

“…We found lower levels of 17q21.31 and 17q11.2 loss/deletion in HER2-low breast cancers than in HER2-0 tumors, which was correlated with a better prognosis in luminal patients. The high correlation among the copy numbers of 17q21.31, 17q11.2 and 17q12 might reflect the 17q12-21 locus (or 17q12-21 amplicon) 41 , 42 or chromothripsis of 17q in ER-positive breast cancers 43 , 44 despite the lack of high amplification in 17q12. Genes located on these peaks, such as NF1 45 , NBR1 46 and BRCA1 47 , 48 , were also considered related to tumor biology and patient survival.…”

Section: Discussionmentioning

confidence: 99%

Molecular features and clinical implications of the heterogeneity in Chinese patients with HER2-low breast cancer

Dai,

Ma,

et al. 2023

Nat Commun

View full text Add to dashboard Cite

The molecular heterogeneity and distinct features of HER2-low breast cancers, particularly in the Chinese population, are not well understood, limiting its precise management in the era of antibody‒drug conjugates. To address this issue, we established a cohort of 434 Chinese patients with HER2-low breast cancer (433 female and one male) and integrated genomic, transcriptomic, proteomic, and metabolomic profiling data. In this cohort, HER2-low tumors are more distinguished from HER2-0 tumors in the hormone receptor–negative subgroup. Within HER2-low tumors, significant interpatient heterogeneity also exists in the hormone receptor–negative subgroup: basal-like tumors resemble HER2-0 disease, and non-basal-like HER2-low tumors mimic HER2-positive disease. These non-basal-like HER2-low tumors are enriched in the HER2-enriched subtype and the luminal androgen receptor subtype and feature PIK3CA mutation, FGFR4/PTK6/ERBB4 overexpression and lipid metabolism activation. Among hormone receptor–positive tumors, HER2-low tumors show less loss/deletion in 17q peaks than HER2-0 tumors. In this work, we reveal the heterogeneity of HER2-low breast cancers and emphasize the need for more precise stratification regarding hormone receptor status and molecular subtype.

show abstract

“…As a result, extensive research has been conducted on indirubin. In a study conducted by Lin et al (2020), the growth-inhibitory effect of three PTHs [perphenazine (PPH), trifluoperazine (TFP), and Thioridazine (THD)] was examined in a group of nine breast cancer patients and immortalized cell lines [ 134 ]. These cell lines exhibited varying levels of TLK2 copy number and protein levels.…”

Section: Factual Considerations and Alternative Modalitiesmentioning

confidence: 99%

Targeting Prostate Cancer, the ‘Tousled Way’

Bhoir

Benedetti

2023

IJMS

View full text Add to dashboard Cite

Androgen deprivation therapy (ADT) has been the mainstay of prostate cancer (PCa) treatment, with success in developing more effective inhibitors of androgen synthesis and antiandrogens in clinical practice. However, hormone deprivation and AR ablation have caused an increase in ADT-insensitive PCas associated with a poor prognosis. Resistance to ADT arises through various mechanisms, and most castration-resistant PCas still rely on the androgen axis, while others become truly androgen receptor (AR)-independent. Our research identified the human tousled-like kinase 1 (TLK1) as a crucial early mediator of PCa cell adaptation to ADT, promoting androgen-independent growth, inhibiting apoptosis, and facilitating cell motility and metastasis. Although explicit, the growing role of TLK1 biology in PCa has remained underrepresented and elusive. In this review, we aim to highlight the diverse functions of TLK1 in PCa, shed light on the molecular mechanisms underlying the transition from androgen-sensitive (AS) to an androgen-insensitive (AI) disease mediated by TLK1, and explore potential strategies to counteract this process. Targeting TLK1 and its associated signaling could prevent PCa progression to the incurable metastatic castration-resistant PCa (mCRPC) stage and provide a promising approach to treating PCa.

show abstract

ERα-related chromothripsis enhances concordant gene transcription on chromosome 17q11.1-q24.1 in luminal breast cancer

Cited by 13 publications

References 74 publications

Tracking telomere fusions through crisis reveals conflict between DNA transcription and the DNA damage response

Tracking telomere fusions through crisis reveals conflict between DNA transcription and the DNA damage response

Molecular features and clinical implications of the heterogeneity in Chinese patients with HER2-low breast cancer

Targeting Prostate Cancer, the ‘Tousled Way’

Contact Info

Product

Resources

About