Spontaneous and Radiation-Induced Chromosome Aberrations in Primary Fibroblasts of Patients With Pediatric First and Second Neoplasms

Zahnreich, Sebastian; Poplawski, Alicia; Hartel, Carola; Eckhard, Lukas; Galetzka, Danuta; Hankeln, Thomas; Löbrich, Markus; Marron, Manuela; Mirsch, Johanna; Ritter, S.; Scholz-Kreisel, Peter; Spix, Claudia; Schmidberger, Heinz

doi:10.3389/fonc.2020.01338

Cited by 5 publications

(7 citation statements)

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“…Our finding that breast tumors from patients with CCS were more likely to be Luminal type‐B than tumors from those without a history of childhood cancer is suggestive of potential differences in tumor biology arising in CCS. While others have also suggested that such biologic differences may exist, to our knowledge detailed studies of genetic differences in colon cancers or melanomas in CCS have not been conducted 17,18 . Our finding that CCS diagnosed with CRC or melanoma did not differ from controls with respect to demographics or stage at presentation is suggestive that such biologic differences may exist in secondary tumors diagnosed in CCS which have yet to be explored.…”

Section: Discussionmentioning

confidence: 60%

“…In addition, it is unclear whether SM in CCS, which may be associated with prior radiation and chemotherapy exposure, may be biologically different from malignancies arising de novo. One prior database study did not detect differences in receptor expression in breast tumors of CCS relative to the general public, 16 but spontaneous chromosomal abnormalities and differences in expression of DNA‐repair genes in CCS diagnosed with a SM have been reported 17,18 …”

Section: Introductionmentioning

confidence: 99%

“…One prior database study did not detect differences in receptor expression in breast tumors of CCS relative to the general public, 16 but spontaneous chromosomal abnormalities and differences in expression of DNA-repair genes in CCS diagnosed with a SM have been reported. 17,18 The purpose of the present study was to compare demographics, disease characteristics, and survival of CCS diagnosed with CRC, melanoma, or BC relative to cancer patients without a history of childhood cancer. Given the notoriously poor compliance by CCS with respect to screening for SM, we hypothesized that CCS diagnosed with a SM would present with more advanced cancer stage and an earlier age at diagnosis than other adult patients diagnosed with the same cancers.…”

Section: Introductionmentioning

confidence: 99%

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Childhood cancer survivors face markedly worse overall survival after diagnosis with breast cancer, melanoma, or colorectal cancer

Lynch

Kane

Fleming

et al. 2021

Journal of Surgical Oncology

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Background Childhood cancer survivors (CCS) are at elevated risk of secondary malignancies (SM). Enhanced screening for SM is recommended, but compliance is poor. We hypothesized that CCS with adult‐onset SM (colorectal cancer [CRC], melanoma, or breast cancer [BC]) would present with more advanced disease and have decreased overall survival (OS). Methods The Surveillance, Epidemiology, and End Results Program was queried for patients diagnosed with cancer at age less than or equal to 18 also diagnosed with adult‐onset CRC, melanoma, or BC. A cohort without a history of prior malignancy was likewise identified. Tumor features and clinical outcomes were compared. Results CCS with a SM (n = 224) were compared with patients without a childhood cancer history (n = 1,392,670). CCS were diagnosed younger (BC = 37.6 vs. 61.3, p < 0.01, CRC = 35.0 vs. 67.1, p < 0.01, melanoma = 29.6 vs. 61.3 years old, p < 0.01). CCS with BC were more likely to have Stage III or IV disease (25.2% vs. 16.5%, p = 0.01). Hormone‐receptor expression also differed; CCS were less likely to develop Luminal A‐type tumors (48.6% vs. 66.9%, p = 0.01). After age‐adjustment, CCS had worse OS (Hazard ratio: CRC = 2.449, p < 0.01, melanoma = 6.503, p < 0.01, BC = 3.383, p < 0.01). Conclusion CCS were younger when diagnosed with a SM. After age‐adjustment, OS was diminished. Heightened surveillance may be necessary for CCS diagnosed with SM.

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Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Childhood cancer survivors face markedly worse overall survival after diagnosis with breast cancer, melanoma, or colorectal cancer

Lynch

Kane

Fleming

et al. 2021

Journal of Surgical Oncology

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“…Thus, there is an urgent need to decipher the etiology of SPMs and to establish predictive clinical biomarkers for individual susceptibility to therapy-related SPMs to adapt oncologic treatments and intensify follow-up with intervention strategies and multidisciplinary care. Next-generation sequencing approaches and affected pathway analysis may unravel molecular genetic markers based on which, e.g., functional bioassays can be performed on minimally invasively obtained normal tissue samples for risk assessments in any given individual [ 437 , 438 , 439 ]. This provides an opportunity to identify high-risk patients who will benefit from close surveillance and ultimately to curtail therapy-related SPMs through a mechanistic understanding of their development by targeted interventions.…”

Section: Discussionmentioning

confidence: 99%

Childhood Cancer: Occurrence, Treatment and Risk of Second Primary Malignancies

Zahnreich

Schmidberger

2021

Cancers

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Cancer represents the leading cause of disease-related death and treatment-associated morbidity in children with an increasing trend in recent decades worldwide. Nevertheless, the 5-year survival of childhood cancer patients has been raised impressively to more than 80% during the past decades, primarily attributed to improved diagnostic technologies and multiagent cytotoxic regimens. This strong benefit of more efficient tumor control and prolonged survival is compromised by an increased risk of adverse and fatal late sequelae. Long-term survivors of pediatric tumors are at the utmost risk for non-carcinogenic late effects such as cardiomyopathies, neurotoxicity, or pneumopathies, as well as the development of secondary primary malignancies as the most detrimental consequence of genotoxic chemo- and radiotherapy. Promising approaches to reducing the risk of adverse late effects in childhood cancer survivors include high precision irradiation techniques like proton radiotherapy or non-genotoxic targeted therapies and immune-based treatments. However, to date, these therapies are rarely used to treat pediatric cancer patients and survival rates, as well as incidences of late effects, have changed little over the past two decades in this population. Here we provide an overview of the epidemiology and etiology of childhood cancers, current developments for their treatment, and therapy-related adverse late health consequences with a special focus on second primary malignancies.

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“…Chromosome instability was reported to contribute to the program of many kinds of cancers including OSCC [4,5]. It was partially responsible for the heterogeneity and chemo-resistance [6].…”

Section: Introductionmentioning

confidence: 99%

Dosage Suppressor of NNF1(DSN1)Promotes Tumour Progression of Oral Squamous Cell Carcinoma(OSCC)Through Remaining High Level of Chromosome Instability

Wang

Jiang

Cui

et al. 2021

Preprint

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Introduction: Dosage suppressor of NNF1 (DSN1) is a component of the kinetochore protein complex which is critical for normal chromosome segregation. Researches showed that DSN1 was upregulated in colorectal carcinoma and hepatocellular carcinoma. However, the biofunction and potential mechanism was still unknown. Materials and methods: We searched The Cancer Genome Atlas (TCGA) database and analyse DSN1 expression pattern in head and neck carcinoma. qRT-PCR and western blot were applied to measure the expression level of DSN1 in OSCC patients and OSCC cell lines. The biological influence of DSN1 was studied using CCK-8, colony formation assay, Transwell migration and invasion assays, the chromosome instability and DNA repair ability were also detected. Results: DSN1 was upregulated in OSCC tissues in both TCGA database and our in-house database. The proliferation, migration and invasion ability decreased in Cal-27 cell line after knocking down of DSN1. The epithelial-mesenchymal transition was activated in DSN1 overexpressed cells. DSN1 confers radio-resistance to OSCC and DSN1 remains high level of chromosome instability and low level of DNA repair. Conclusion: Taken above, our results indicate that the upregulated DSN1 is positively associated with prognosis in OSCC. Our findings indicate that DSN1 promotes OSCC cell proliferation, migration and invasion and radio resistance and remains OSCC with high level of chromosome instability.

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Spontaneous and Radiation-Induced Chromosome Aberrations in Primary Fibroblasts of Patients With Pediatric First and Second Neoplasms

Cited by 5 publications

References 58 publications

Childhood cancer survivors face markedly worse overall survival after diagnosis with breast cancer, melanoma, or colorectal cancer

Childhood cancer survivors face markedly worse overall survival after diagnosis with breast cancer, melanoma, or colorectal cancer

Childhood Cancer: Occurrence, Treatment and Risk of Second Primary Malignancies

Dosage Suppressor of NNF1(DSN1)Promotes Tumour Progression of Oral Squamous Cell Carcinoma(OSCC)Through Remaining High Level of Chromosome Instability

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