Clinical and Molecular Characteristics of Squamous Cell Carcinomas From Fanconi Anemia Patients

Zeeburg, Hester J.T. van; Snijders, Peter J.F.; Wu, Thijs; Gluckman, Éliane; Soulier, Jean; Surrallés, Jordi; Castellà, María; Wal, Jacqueline E. van der; Wennerberg, Johan; Califano, Joseph A.; Velleuer, Eunike; Dietrich, Ralf; Ebell, Wolfram; Bloemena, Elisabeth; Joenje, Hans; Leemans, C. René; Brakenhoff, Ruud H.

doi:10.1093/jnci/djn366

Cited by 101 publications

(91 citation statements)

References 20 publications

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“…This is a significant tumour burden and several patients present with multiple independent primary tumours. The majority of solid tumours are squamous cell carcinomas of head and neck, oesophagus and the anogenital region [32,37,38]. Patients diagnosed in adulthood often have no features of FA except genomic instability and predisposition to neoplasia.…”

Section: Neoplasiamentioning

confidence: 99%

The Fanconi anaemia pathway orchestrates incisions at sites of crosslinked DNA

Crossan

Patel

2011

The Journal of Pathology

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Fanconi anaemia (FA) is a rare, autosomal recessive, genetically complex, DNA repair deficiency syndrome in man. Patients with FA exhibit a heterogeneous spectrum of clinical features. The most significant and consistent phenotypic characteristics are stem cell loss, causing progressive bone marrow failure and sterility, diverse developmental abnormalities and a profound predisposition to neoplasia. To date, 15 genes have been indentified, biallelic disruption of any one of which results in this clinically defined syndrome. It is now apparent that all 15 gene products act in a common process to maintain genome stability. At the molecular level, a fundamental defect in DNA repair underlies this complex phenotype. Cells derived from FA patients spontaneously accumulate broken chromosomes and exhibit a marked sensitivity to DNA-damaging chemotherapeutic agents. Despite complementation analysis defining many components of the FA DNA repair pathway, no direct link to DNA metabolism was established until recently. First, it is now evident that the FA pathway is required to make incisions at the site of damaged DNA. Second, a specific component of the FA pathway has been identified that regulates nucleases previously implicated in DNA interstrand crosslink repair. Taken together, these data provide genetic and biochemical evidence that the FA pathway is a bona fide DNA repair pathway that directly mediates DNA repair transactions, thereby elucidating the specific molecular defect in human Fanconi anaemia.

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Section: Neoplasiamentioning

confidence: 99%

The Fanconi anaemia pathway orchestrates incisions at sites of crosslinked DNA

Crossan

Patel

2011

The Journal of Pathology

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“…For example, patients suffering from Li Fraumeni syndrome have a genetic predisposition to develop multiple tumours due to an inherited mutation in one allele of the p53 locus which results in susceptibility to develop sarcomas and other tumours in successive generations. Patients suffering from Fanconi anaemia, a recessively inherited disease characterized by congenital anomalies and bone marrow failure, have a predisposition to develop cancer, particularly squamous cell carcinomas in the head and neck and anogenital regions (54). These and other genetic factors such as oncogenes may well help explain differing susceptibilities of individual people to cancer -causing the varying effects of known risk factors such as tobacco and alcohol.…”

Section: -Social and Economic Status (Ses)mentioning

confidence: 99%

Oral cancer aetiopathogenesis; past, present and future aspects

Scully¹

2011

Med Oral

101

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Oral cancer appears to be increasing in incidence, and mortality has hardly improved over the past 25 years. Better understanding of the aetiopathogenesis should lead to more accurate and earlier diagnosis and more effective treatments with fewer adverse effects. Cancer is the result of DNA mutations arising spontaneously and from the action of various mutagens, especially in tobacco and alcohol. A sequence of genetic changes leads eventually to loss of growth control and autonomy. Countering these changes are mechanisms to metabolise carcinogens, repair DNA damage, control growth, and defend against cancer. Cancer is a consequence of an interaction of these many factors. Diagnosis is increasingly aided by detection of cellular and now molecular changes. Treatment is increasingly looking towards chemotherapy and now gene therapy. However, there is no doubt that prevention is the most important aspect, particularly patient education and the reduction of lifestyle risk habits and environmental factors.

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“…[1][2][3] The prevalence of the disease is approximately 1:350,000 births, with an equal distribution in both genders. 1,4 Haematopoietic stem cell transplantation (HSCT) is the only curative treatment for bone marrow failure in FA.…”

Section: Introductionmentioning

confidence: 99%

Exfoliative Cytology in the Oral Mucosa of Patients with Fanconi Anaemia: A Morphometric Approach

Machado¹,

D'Agulham²,

Chaiben³

et al. 2017

J Dent Indones

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Patients with Fanconi anaemia (FA) are prone to develop squamous cell carcinomas at an early age. Exfoliative cytology can be used to detect changes to the health of the oral mucosa. Objective: The aim of this study was to evaluate morphometrical and morphological changes using exfoliative cytology and to analyse and quantify the proliferative activity using silver nucleolar organiser regions (AgNOR) in epithelial cells of the tongue in FA patients, after haematopoietic stem cell transplantation (HSCT). Methods: Oral smears were collected from the tongues of 20 FA children and adolescents after haematopoietic stem cell transplantation (FA) and 20 healthy children (C) using exfoliative cytology. The smears were stained using the Papanicolaou technique and silver impregnation. The cells were morphologically analysed and the nuclear area (NA), the cytoplasmic area (CA), and the nucleusto-cytoplasm area ratio (NA/CA) were calculated. Results: Mean values for the FA and C groups were: NA (71.85 and 55.21µm²; p< 0.01); CA (2127.48 and 1441.61µm²; p< 0.01); NA/CA (0.03 and 0.04; p< 0.01), respectively. A significant increase in the NA and CA for the FA group (p< 0.01) was seen, and an alteration in the NA/CA ratio. No morphological differences were found between the groups. Class I smears were predominant in both groups. No differences were found between the groups for the mean values of AgNORs per nucleus. Conclusion: This study suggests that morphological changes occurred in the oral epithelium cells of children and adolescents with Fanconi anaemia when subjected to HSCT.

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Clinical and Molecular Characteristics of Squamous Cell Carcinomas From Fanconi Anemia Patients

Cited by 101 publications

References 20 publications

The Fanconi anaemia pathway orchestrates incisions at sites of crosslinked DNA

The Fanconi anaemia pathway orchestrates incisions at sites of crosslinked DNA

Oral cancer aetiopathogenesis; past, present and future aspects

Exfoliative Cytology in the Oral Mucosa of Patients with Fanconi Anaemia: A Morphometric Approach

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