A Patient with 17 Primary Tumours and a Germ Line Mutation in TP53: Tumour Induction by Adjuvant Therapy?

Nutting, Chris; Camplejohn, Richard S.; Gilchrist, R; Tait, David L.; Blake, P.; Knee, G.; Yao, Weinan; Ross, Gillian; Fisher, C.J.; Eeles, Ros

doi:10.1053/clon.2000.9179

Cited by 18 publications

(14 citation statements)

References 15 publications

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“…And yet Li and Fraumeni 13 , as well as others 12,[14][15][16][17][18][19][20] , observed cancers developing more frequently in patients after rt. For example, Heymann et al 14 noted 8 new cancers in 6 patients treated with adjuvant breast rt, compared with 1 new cancer in 2 patients treated without rt.…”

Section: Discussionmentioning

confidence: 89%

Lack of Toxicity in a Patient with Germline Tp53 Mutation Treated with Radiotherapy

Wong¹,

Han²

2014

Current Oncology

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patient population are scarce because of concerns that normal cells with mutated TP53 are more sensitive to rt than are cells without TP53 mutations and that rt will induce new primary cancers in these (often young) patients. CASE DESCRIPTIONA 61-year-old woman who had been diagnosed with stage ib uterine leiomyosarcoma in 2000 and with stage T2N0 papillary thyroid cancer in 2001 was referred for consideration of palliative rt to a right upper quadrant abdominal metastasis from her leiomyosarcoma that caused occasional pain and intermittent small-bowel obstruction. The leiomyosarcoma had initially been treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by adjuvant pelvic rt using a 4-field box technique (45 Gy in 25 fractions). The thyroid cancer was managed with thyroidectomy and adjuvant radioactive iodine [0.75 mCi (27.75 MBq)].The patient had no evidence of recurrence until 2007, when she developed biopsy-proven metastatic leiomyosarcoma to the lungs, heart, bone, and upper abdomen (Figure 1). She was initiated on doxorubicin and ifosfamide, which was followed by gemcitabine in the subsequent 2 years. Follow-up computed tomography imaging 3 months after the 18th cycle of gemcitabine revealed a lytic lesion of her right proximal humerus, which was subsequently treated with palliative rt for pain (35.25 Gy in 15 fractions) in 2010.The patient underwent further chemotherapy on trial (phase iii, eribulin vs. dacarbazine; search for NCT01327885 at http://clinicaltrials.gov/) and received dacarbazine until her current admission. Since 2010, she has also undergone 3 bile stent procedures secondary to the enlarging right-sided upper abdominal mass, which, at the time of the current consultation, measured 18.0×18.0×9.4 cm (Figure 2).During the course of the patient's palliative rt to the humerus, her infant granddaughter was ABSTRACT Li-Fraumeni syndrome is an autosomal dominant disorder characterized by germline TP53 mutation and increased susceptibility to cancer. Despite certain in vitro findings and a theoretical rationale for patients with TP53 mutation to be more radiosensitive and more prone to developing radiotherapy (rt)-induced secondary malignancies, corresponding clinical data remain elusive. Here, we report the case of a woman with TP53 mutation who was treated with adjuvant pelvic rt for stage ib uterine leiomyosarcoma in 2000, with radioactive iodine for papillary thyroid cancer in 2001, and with palliative rt to the humerus in 2010 for metastatic uterine leiomyosarcoma. She has not developed any acute or late rt-related toxicity, nor any secondary malignancies, since her first rt treatment. The literature review describes the potential risks and benefits of using irradiation in patients with TP53 mutation.

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Section: Discussionmentioning

confidence: 89%

Lack of Toxicity in a Patient with Germline Tp53 Mutation Treated with Radiotherapy

Wong¹,

Han²

2014

Current Oncology

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“…There is evidence to suggest that a prophylactic mastectomy in women with a high risk of breast cancer is beneficial, and may have been of benefit to the patient in this report [10]. Several cases of radiation-induced secondary malignancies have been reported, and there are many reviews on the controversial effects of radiation in LFS patients [11][12][13]. If the mutation status had been revealed, the patient and the medical staff according to their policy [15].…”

Section: Discussionmentioning

confidence: 99%

Genetic Counseling Can Influence the Course of a Suspected Familial Cancer Syndrome Patient: From a Case of Li-Fraumeni Like Syndrome with a Germline Mutation in the TP53 Gene

et al. 2008

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“…Additionally, it was reported that individuals carrying both the TP53 Pro and MDM2 SNP G alleles were at increased risk of therapy-related acute myeloid leukemia after alkylating therapy (49). A similar situation could have occurred in an LFS patient who had accumulated a number of mutations, explaining the 17 different cancer types he suffered following different treatments (50).…”

Section: ------------------------------------------------------------mentioning

confidence: 92%

Heterozygous TP53stop146/R72P fibroblasts from a Li-Fraumeni syndrome patient with impaired response to DNA damage

Moura

Kavalec²,

Doghman³

et al. 2010

Int J Oncol

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Abstract. The Li-Fraumeni syndrome (LFS) is a rare autosomal dominant hereditary cancer syndrome, characterized by a wide spectrum of neoplasms, occurring in children and young adults. The identification of germline TP53 mutations in LFS has given rise to a number of in vitro studies using cultures of cancer cells and non-tumoral fibroblasts presenting germline TP53 mutations. In the present study, we performed a detailed documentation of the pedigree of an LFS family with a comprehensive analysis of genotype-phenotype correlations. We sequenced the TP53 gene and verified that the proband carries a germline nonsense mutation in codon 146 in one allele, the TP53 Arg72Pro polymorphism in the second, and other intronic polymorphisms in the TP53 gene. In order to investigate the disruption of the p53 function in a patient presenting this mutation and the TP53 Arg72Pro polymorphism who had so far suffered five malignant tumors and a benign meningioma, we tested her fibroblasts in response to DNA damage by evaluating the proliferation rate, apoptosis, and disruption of the TP53 pathway. The proband's heterozygous fibroblasts were not as efficient as control fibroblasts or those of her mother, who carried only the TP53 Arg72Pro polymorphism, in causing cell arrest and cell death after DNA damage, which was correlated with diminished TP21 protein levels.

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A Patient with 17 Primary Tumours and a Germ Line Mutation in TP53: Tumour Induction by Adjuvant Therapy?

Cited by 18 publications

References 15 publications

Lack of Toxicity in a Patient with Germline Tp53 Mutation Treated with Radiotherapy

Lack of Toxicity in a Patient with Germline Tp53 Mutation Treated with Radiotherapy

Genetic Counseling Can Influence the Course of a Suspected Familial Cancer Syndrome Patient: From a Case of Li-Fraumeni Like Syndrome with a Germline Mutation in the TP53 Gene

Heterozygous TP53stop146/R72P fibroblasts from a Li-Fraumeni syndrome patient with impaired response to DNA damage

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