NFIB is a potential target for estrogen receptor‐negative breast cancers

Moon, Hyeong‐Gon; Hwang, Kihwan; Kim, Jeong Ah; Kim, Hee Sung; Lee, Min Joo; Jung, Eun Mi; Ko, Eunyoung; Han, Wonshik; Noh, Dong‐Young

doi:10.1016/j.molonc.2011.08.002

Cited by 52 publications

(46 citation statements)

References 26 publications

(33 reference statements)

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“…NFIB is reported to behave as an oncogene in small cell lung cancer(33) and is overexpressed in estrogen receptor-negative breast cancer. (34) It is conceivable, therefore, that there is a role for NFIB overexpression in ACC oncogenesis. Taken together with the high prevalence of NFIB fusion genes, this constellation of findings suggest that NFIB may be contribute more significantly to ACC biology than has been previously appreciated.…”

Section: Discussionmentioning

confidence: 99%

Whole-Genome Sequencing of Salivary Gland Adenoid Cystic Carcinoma

Rettig

Talbot

Sausen

et al. 2016

Cancer Prevention Research

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Adenoid cystic carcinomas (ACCs) of the salivary glands are challenging to understand, treat, and cure. To better understand the genetic alterations underlying the pathogenesis of these tumors, we performed comprehensive genome analyses of 25 fresh-frozen tumors, including whole genome sequencing, expression and pathway analyses. In addition to the well-described MYB-NFIB fusion which was found in 11 tumors (44%), we observed five different rearrangements involving the NFIB transcription factor gene in seven tumors (28%). Taken together, NFIB translocations occurred in 15 of 25 samples (60%, 95%CI=41–77%). In addition, mRNA expression analysis of 17 tumors revealed overexpression of NFIB in ACC tumors compared with normal tissues (p=0.002). There was no difference in NFIB mRNA expression in tumors with NFIB fusions compared to those without. We also report somatic mutations of genes involved in the axonal guidance and Rho family signaling pathways. Finally, we confirm previously described alterations in genes related to chromatin regulation and Notch signaling. Our findings suggest a separate role for NFIB in ACC oncogenesis and highlight important signaling pathways for future functional characterization and potential therapeutic targeting.

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Section: Discussionmentioning

confidence: 99%

Whole-Genome Sequencing of Salivary Gland Adenoid Cystic Carcinoma

Rettig

Talbot

Sausen

et al. 2016

Cancer Prevention Research

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“…A focal high-level amplification on Chromosome 9p encompassed JAK2 and PDL1 (also known as CD274 or B7-H1 ) together with other genes implicated in carcinogenesis (Fig. 1; Kietz et al 2009; Moon et al 2011; Zhang et al 2012; Hoffman et al 2014; Jovanovic et al 2014; Kim et al 2015). …”

Section: Resultsmentioning

confidence: 99%

Integration of genomics and histology revises diagnosis and enables effective therapy of refractory cancer of unknown primary with PDL1 amplification

Gröschel

Bommer

Hutter

et al. 2016

Cold Spring Harb Mol Case Stud

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Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision-making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multiagent chemotherapy. Molecular profiling within a clinical whole-exome and transcriptome sequencing program revealed a heterozygous, highly amplified KRAS G12S mutation, compound-heterozygous TP53 mutation/deletion, high mutational load, and focal high-level amplification of Chromosomes 9p (including PDL1 [CD274] and JAK2) and 10p (including GATA3). Integrated analysis of molecular data and histopathology provided a rationale for immune checkpoint inhibitor (ICI) therapy with pembrolizumab, which resulted in rapid clinical improvement and a lasting partial remission. Histopathological analyses ruled out sarcoma and established the diagnosis of a poorly differentiated adenocarcinoma. Although neither histopathology nor molecular data were able to pinpoint the tissue of origin, our analyses established several differential diagnoses including triple-negative breast cancer (TNBC). We analyzed 157 TNBC samples from The Cancer Genome Atlas, revealing PDL1 copy number gains coinciding with excessive PDL1 mRNA expression in 24% of cases. Collectively, these results illustrate the impact of multidimensional tumor profiling in cases with nondescript histology and immunophenotype, show the predictive potential of PDL1 amplification for immune checkpoint inhibitors (ICIs), and suggest a targeted therapeutic strategy in Chromosome 9p24.1/PDL1-amplified cancers.

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“…For example, NFIB is highly expressed in small-cell lung cancer and triplenegative breast cancer compared to normal tissues. Consequently, repression of apoptosis promotes cell proliferation (Dooley et al, 2011;Moon et al, 2011). These observations indicate that NFIB may have distinct roles in different cancers, which may depend on the activation or repression of downstream signaling pathways.…”

Section: Discussionmentioning

confidence: 99%