<i>HMGA2</i> overexpression in non‐small cell lung cancer

Meyer, Britta; Loeschke, Siegfried; Schultze, Anke; Weigel, Thomas; Sandkamp, M.; Goldmann, Torsten; Vollmer, Ekkehard; Bullerdiek, Jörn

doi:10.1002/mc.20235

Cited by 158 publications

(122 citation statements)

References 41 publications

(45 reference statements)

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“…This better prognosis seems specific to adipose tumors as alterations of HMGA2 have been associated with bad prognosis in several other tumor types, mainly carcinomas. [24][25][26] Our observations are reminiscent of the positive role of HMGA2 in adipocytic differentiation. Indeed, hmga2 − / − mice show a pygmy phenotype characterized by a small size and a deficiency in fat tissue, 27 whereas overexpression of a truncated HMGA2: a prognostic biomarker in liposarcomas hmga2 gene induces gigantism and lipomatosis in murine models.…”

Section: Discussionmentioning

confidence: 66%

Prognostic value of HMGA2, CDK4, and JUN amplification in well-differentiated and dedifferentiated liposarcomas

et al. 2015

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HMGA2, CDK4, and JUN genes have been described as frequently coamplified with MDM2 in atypical lipomatous tumor, well-differentiated liposarcoma, and dedifferentiated liposarcoma. We studied the frequency of amplification of these genes in a series of 48 dedifferentiated liposarcomas and 68 atypical lipomatous tumors/well-differentiated liposarcomas. We correlated their amplification status with clinicopathological features and outcomes. Histologically, both CDK4 (P = 0.007) and JUN (P = 0.005) amplifications were associated with dedifferentiated liposarcoma, whereas amplification of the proximal parts of HMGA2 (5′-untranslated region (UTR) and exons 1-3) was associated with atypical lipomatous tumor/well-differentiated liposarcoma (P = 0.01). CDK4 amplification was associated with axial tumors. Amplification of 5′-UTR and exons 1-3 of HMGA2 was associated with primary status and grade 1. Shorter overall survival was correlated with: age 464 years (P = 0.03), chemotherapy used in first intent (Po0.001), no surgery (P = 0.003), grade 3 (Po0.001), distant metastasis (Po0.001), node involvement (P = 0.006), and CDK4 amplification (P = 0.07). In multivariate analysis, distant metastasis (HR = 8.8) and grade 3 (HR = 18.2) were associated with shorter overall survival. A shorter recurrence-free survival was associated with dedifferentiated liposarcoma (Po0.001), grade 3 (Po0.001), node involvement (Po0.001), distant metastasis (P = 0.02), recurrent status (P = 0.009), axial location (P = 0.001), and with molecular features such as CDK4 (P = 0.05) and JUN amplification (P = 0.07). Amplification of 5′-UTR and exons 1-3 (P = 0.08) and 3′-UTR (P = 0.01) of HMGA2 were associated with longer recurrence-free survival. Distant metastasis was associated with shorter recurrence-free survival (HR = 5.8) in multivariate analysis. Dedifferentiated liposarcoma type was associated with axial location, grade 3 and recurrent status. In conclusion, we showed that the amplification of HMGA2 was associated with the atypical lipomatous tumor/well-differentiated liposarcoma histological type and a good prognosis, whereas CDK4 and JUN amplifications were associated with dedifferentiated liposarcoma histology and a bad prognosis. In addition, we also provided the first description of the molecular evolution of a well-differentiated liposarcoma into four successive dedifferentiated liposarcoma relapses, which was consistent with our general observations.

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Section: Discussionmentioning

confidence: 66%

Prognostic value of HMGA2, CDK4, and JUN amplification in well-differentiated and dedifferentiated liposarcomas

et al. 2015

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“…Several recent studies have implied that HMGA2 expression correlated with lymph node metastases and tumor progression in several solid tumors. [28][29][30] HMGA2 expression in oral squamous cell carcinoma has also been reported. 31 Our results are consistent with previous reports.…”

Section: Discussionmentioning

confidence: 87%

Stem cell self-renewal factors Bmi1 and HMGA2 in head and neck squamous cell carcinoma: clues for diagnosis

Yamazaki

Mori

Yazawa

et al. 2013

Laboratory Investigation

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Head and neck squamous cell carcinoma (HNSCC) includes both morphological and functional cellular heterogeneity, as would be expected if it arose from dysregulated stem or progenitor cells as opposed to the simple clonal expansion of a mutated cell; however, stemness molecule expression levels and distribution in HNSCC remain unclear. To clarify this, stemness molecule expressions were determined in HNSCC, as well as their properties and prognosis. Two protooncogenic chromatin regulators, Bmi-1 and high-mobility-group A2 (Hmga2), were identified in 12 pair cases of HNSCC tumor regions by comparison with their non-cancerous background tissues using cDNA microarray. Both Bmi-1 and Hmga2 are known to promote stem cell self-renewal by negatively regulating the expressions of Ink4a and Arf tumor suppressors. Despite similar targets, Bmi-1 protein was expressed in an early cancerous region and HMGA2 protein was expressed in a region showing more progression. Similarly, Bmi1 expression had no significance with regard to overall survival (P ¼ 0.67), whereas HMGA2 expression was associated with decreased overall survival (P ¼ 0.05). Quantitative realtime reverse transcription polymerase chain reaction analyses also correlated with protein levels. These findings suggest that Bmi-1 is an early detection marker to distinguish cancerous from non-cancerous regions, whereas HMGA2 is presumed to be a tumor prognosis marker. Among our HNSCC analyses, these stemness molecules expressed fewer primitive rare cells in the tumor than all other cells in the tumor. HNSCC cells with high expression of stemness molecules partly behave like stem cells. Head and neck squamous cell carcinoma (HNSCC) is typically associated with virus infection, persistent chronic inflammation, and tobacco and alcohol use. Survival rates have changed in the last 40 years because of reductions in these factors; 1 however, the mortality rate remains high because advanced and recurrent locoregional control is difficult in many cases. Better understanding of the biology of HNSCC is required to define relevant targets and to develop novel therapeutic approaches. HNSCCs have both morphological and functional cellular heterogeneity, as would be expected if they arose from dysregulated stem or progenitor cells as opposed to the simple clonal expansion of a mutated cell. 2 Recently, numerous reports have shown support for the 'cancer stem cell' theory in many types of tumor, including HNSCC. 3,4,5 Acute and chronic myeloid leukemias follow the cancer stem cell model. Both tumors show robustly hematopoietic hierarchical organization in the tumor cells; 6,7 however, for solid cancers such as squamous cell carcinoma, it is not clear how generalizable the cancer stem cell model is. Not all cancer cells have the same capacity to proliferate. 8 In some cancers, most cancer cells appear to have limited ability to proliferate, while in the same tumors, stochastic minority populations of stemness molecules highly expressed in cancer as a 'stem-like cancer' retain the capacity...

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“…HMGA2 has also been implicated in cancer. HMGA2 overexpression has been found in lung and pancreatic carcinomas (55,56). HMGA2 protein overexpression is usually met with the presence of metastasis and reduced survival of the cancer patient (54).…”

Section: Hmga2mentioning

confidence: 99%

MicroRNA Regulation of Cancer Stem Cells and Therapeutic Implications

DeSano

2009

AAPS J

143

107

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Abstract. MicroRNAs (miRNAs) are a class of endogenous non-protein-coding RNAs that function as important regulatory molecules by negatively regulating gene and protein expression via the RNA interference (RNAi) machinery. MiRNAs have been implicated to control a variety of cellular, physiological, and developmental processes. Aberrant expressions of miRNAs are connected to human diseases such as cancer. Cancer stem cells are a small subpopulation of cells identified in a variety of tumors that are capable of self-renewal and differentiation. Dysregulation of stem cell self-renewal is a likely requirement for the initiation and formation of cancer. Furthermore, cancer stem cells are a very likely cause of resistance to current cancer treatments, as well as relapse in cancer patients. Understanding the biology and pathways involved with cancer stem cells offers great promise for developing better cancer therapies, and might one day even provide a cure for cancer. Emerging evidence demonstrates that miRNAs are involved in cancer stem cell dysregulation. Recent studies also suggest that miRNAs play a critical role in carcinogenesis and oncogenesis by regulating cell proliferation and apoptosis as oncogenes or tumor suppressors, respectively. Therefore, molecularly targeted miRNA therapy could be a powerful tool to correct the cancer stem cell dysregulation.

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HMGA2 overexpression in non‐small cell lung cancer

Cited by 158 publications

References 41 publications

Prognostic value of HMGA2, CDK4, and JUN amplification in well-differentiated and dedifferentiated liposarcomas

Prognostic value of HMGA2, CDK4, and JUN amplification in well-differentiated and dedifferentiated liposarcomas

Stem cell self-renewal factors Bmi1 and HMGA2 in head and neck squamous cell carcinoma: clues for diagnosis

MicroRNA Regulation of Cancer Stem Cells and Therapeutic Implications

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