Li-Fraumeni syndrome: cancer risk assessment and clinical management

McBride, Kate A; Ballinger, Mandy L.; Killick, Emma; Kirk, Judy; Tattersall, Martin H. N.; Eeles, Rosalind; Thomas, David M.; Mitchell, Gillian

doi:10.1038/nrclinonc.2014.41

Cited by 217 publications

(190 citation statements)

References 109 publications

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“…Human patients often present with neurological symptoms such as headaches and seizures, and despite the vast amount of genomic data and novel therapies now available, GBMs recur quickly and aggressively after resection and often lead to death [124]. Several of the human cancer predisposition syndromes include gliomas in their clinical spectrum [127][128][129][130][131][132][133], supporting the genetic risk for development of these tumours.…”

Section: (I) Meningiomamentioning

confidence: 99%

Comparative oncology: what dogs and other species can teach us about humans with cancer

Schiffman

Breen

2015

Phil. Trans. R. Soc. B

293

315

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One contribution of 18 to a theme issue 'Cancer across life: Peto's paradox and the promise of comparative oncology'. Over 1.66 million humans (approx. 500/100 000 population rate) and over 4.2 million dogs (approx. 5300/100 000 population rate) are diagnosed with cancer annually in the USA. The interdisciplinary field of comparative oncology offers a unique and strong opportunity to learn more about universal cancer risk and development through epidemiology, genetic and genomic investigations. Working across species, researchers from human and veterinary medicine can combine scientific findings to understand more quickly the origins of cancer and translate these findings to novel therapies to benefit both human and animals. This review begins with the genetic origins of canines and their advantage in cancer research. We next focus on recent findings in comparative oncology related to inherited, or genetic, risk for tumour development. We then detail the somatic, or genomic, changes within tumours and the similarities between species. The shared cancers between humans and dogs that we discuss include sarcoma (osteosarcoma, soft tissue sarcoma, histiocytic sarcoma, hemangiosarcoma), haematological malignancies (lymphoma, leukaemia), bladder cancer, intracranial neoplasms (meningioma, glioma) and melanoma. Tumour risk in other animal species is also briefly discussed. As the field of genomics advances, we predict that comparative oncology will continue to benefit both humans and the animals that live among us.

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Section: (I) Meningiomamentioning

confidence: 99%

Comparative oncology: what dogs and other species can teach us about humans with cancer

Schiffman

Breen

2015

Phil. Trans. R. Soc. B

293

315

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“…LFS is a rare autosomal dominant syndrome, in which patients are predisposed to a wide variety of cancer types, with a young age at onset of malignancies, and the potential for multiple primary cancer sites during the affected individual's lifetime (57). A Li-Fraumeni-like (LFL) syndrome with less stringent criteria than LFS was subsequently described.…”

Section: Germline Tp53 Variants In Hereditary Cancer Predisposition Smentioning

confidence: 99%

Recommended Guidelines for Validation, Quality Control, and Reporting of TP53 Variants in Clinical Practice

et al. 2017

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Accurate assessment of TP53 gene status in sporadic tumors and in the germline of individuals at high risk of cancer due to Li-Fraumeni Syndrome (LFS) has important clinical implications for diagnosis, surveillance, and therapy. Genomic data from more than 20,000 cancer genomes provide a wealth of information on cancer gene alterations and have confirmed TP53 as the most commonly mutated gene in human cancer. Analysis of a database of 70,000 TP53 variants reveals that the two newly discovered exons of the gene, exons 9b and 9g, generated by alternative splicing, are the targets of inactivating mutation events in breast, liver, and head and neck tumors. Furthermore, germline rearrangements in intron 1 of TP53 are associated with LFS and are frequently observed in sporadic osteosarcoma. In this context of constantly growing genomic data, we discuss how screening strategies must be improved when assessing TP53 status in clinical samples. Finally, we discuss how TP53 alterations should be described by using accurate nomenclature to avoid confusion in scientific and clinical reports.

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“…Hasta el momento, son pocos los casos reportados de cáncer de mama masculino asociados al síndrome de Li-Fraumeni. La información y las recomendaciones para el tratamiento de estos pacientes se basan en series de casos, por lo que es necesario hacer estudios clínicos aleatorios que evalúen estrategias de cribado en portadores de mutaciones en la línea germinal del gen Tp53, dada la baja penetrancia de este polimorfismo (21).…”

Section: Síndrome De Li-fraumeni Y Cáncer De Senounclassified

Síndrome de Li-Fraumeni

Ossa

Molina

Cock-Rada³

2016

biomedica

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Contribución de los autores:Carlos Andrés Ossa: médico tratante, coordinación del estudio clínico y paraclínico del paciente Gustavo Molina: médico tratante Alicia María Cock-Rada: valoración oncogenética e interpretación de los resultados moleculares Todos los autores participaron en la escritura del manuscrito y en la búsqueda de bibliografía. El síndrome de Li-Fraumeni se caracteriza por la aparición de tumores en múltiples órganos, generalmente a temprana edad. Esta condición hereditaria es causada por mutaciones germinales en el gen TP53, que codifica el gen supresor tumoral p53. Se presenta el caso de una paciente de 31 años con diagnóstico clínico y molecular de síndrome de Li-Fraumeni, que presentó dos tumores sincrónicos a los 31 años: un leiomiosarcoma de antebrazo y un tumor filoides de mama. Tenía el antecedente de un hijo con diagnóstico de carcinoma cortical suprarrenal a los tres años, que falleció a los cinco años debido a la enfermedad. Además, su abuela y su bisabuela maternas habían fallecido de cáncer gástrico a los 56 y 60 años, respectivamente, y la madre y una hermana de su abuelo materno presentaron cáncer de mama pasados los 60 y los 40 años de edad, respectivamente. Después de una asesoría genética, se ordenó hacer la secuenciación completa y el análisis de duplicaciones y deleciones en el gen TP53. El estudio molecular en una muestra de ADN proveniente de linfocitos de sangre periférica reveló la mutación germinal c.527G>T (p.Cys176Phe) en el exón 5 del gen, mutación deletérea descrita anteriormente en tejidos tumorales. Hasta donde se sabe, este es el primer caso que se publica en Colombia de síndrome de Li-Fraumeni con diagnóstico molecular confirmado. El diagnóstico y el manejo del síndrome de Li-Fraumeni deben estar a cargo de un equipo multidisciplinario, y debe contarse con asesoría genética para el paciente y sus familiares. Síndrome de Li-FraumeniPalabras clave: síndrome de Li-Fraumeni, gen TP53, asesoramiento genético, síndromes neoplásicos hereditarios, tumor filoides, Colombia. doi: http://dx.doi.org/10.7705/biomedica.v36i3.2793 Li-Fraumeni syndromeThe Li-Fraumeni syndrome is characterized clinically by the appearance of tumors in multiple organs generally at an early age. This hereditary condition is caused by germinal mutations in the TP53 gene, which codifies for the tumoural suppressor gene p53. We present the case of a patient aged 31 with clinical and molecular diagnosis of Li-Fraumeni syndrome who presented two synchronous tumors: a leiomyosarcoma on the forearm and a phyllodes breast tumour. She had a family history of cancer, including a son diagnosed with a cortical adrenal carcinoma when he was three years old, who died at five from the disease. Furthermore, her maternal grandmother and great-grandmother died of stomach cancer at 56 and 60 years old, respectively, while her other greatgrandmother and a great aunt presented with breast cancer at the ages of 60 and 40, respectively. After genetic counseling, complete sequencing and analysis of duplications and delet...

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Li-Fraumeni syndrome: cancer risk assessment and clinical management

Cited by 217 publications

References 109 publications

Comparative oncology: what dogs and other species can teach us about humans with cancer

Comparative oncology: what dogs and other species can teach us about humans with cancer

Recommended Guidelines for Validation, Quality Control, and Reporting of TP53 Variants in Clinical Practice

Síndrome de Li-Fraumeni

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