Composite Adrenocortical Carcinoma and Neuroblastoma in an Infant With a TP53 Germline Mutation: A Case Report and Literature Review

Tang, Yuejia; Yu, Tingting; Ma, Jing; Zhou, Ying; Xu, Min; Gao, Yijin

doi:10.1097/mph.0000000000001205

Cited by 4 publications

(9 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Li-Fraumeni syndrome (LFS) is a familial cancer syndrome associated with multiple malignancies and TP53 gene mutation. [3] This case report comes close to being labeled as LFS.…”

Section: Introductionmentioning

confidence: 59%

“…Three other reports were found where the patients are aged 6, 8, and 10 months. [3,9,10] There are multiple cases of neuroblastoma which are reported with TP53 gene mutation [Table 2]. There are six reported cases of TP53 mutation with adrenocortical cancer (ACC) and neuroblastoma.…”

Section: Discussionmentioning

confidence: 99%

“…Because the child has three histologically distinct malignancies, gene mutation studies were done which revealed germline TP53 gene mutation (c. C530G, p. Pro177Arg) with allelic ID 468390 and MLH3 gene (c. G2221T, p. Val741Phe) mutations. Interphase fluorescent in situ hybridization (FISH) technique revealed a 15-fold increase of NMYC signals to chromosome enumeration probe signals, confirming MLPA) assay was also performed on the neuroblastoma tissue to check for segmental chromosomal anomalies on chromosomes 1, 2,3,4,7,9,11,12, and 17 [Table …”

mentioning

confidence: 99%

See 2 more Smart Citations

A case of synchronous malignancy with novel missense mutation in a child: Is this Li-Fraumeni syndrome or a novel case masquerading as Li-Fraumeni syndrome??

Raj

Redkar

Tewari

et al. 2020

Indian Journal of Medical and Paediatric Oncology

View full text Add to dashboard Cite

We report the case of an 11-month-old child who presented with a change in voice, increased weight, and hirsutism, who was also found to have elevated levels of serum cortisol and testosterone, showing three synchronous malignancies in the liver, left adrenal gland, and posterior mediastinum. Clinical exome sequencing report revealed germline TP53 (P177A) and MLH3 (V741P) mutations with NMYC positive neuroblastoma. At the outset, this may look like a Li-Fraumeni syndrome (LFS) with TP53 germline mutation but lacks other features to be termed as LFS or Li-Fraumeni-like syndrome. The gene mutation variant found in this case (P177A) is a novel missense mutation which has never been reported, and the MLH3 gene mutation variant V741P has not been previously associated with any of the malignancies seen in this child.

show abstract

“…Li-Fraumeni syndrome (LFS) is a familial cancer syndrome associated with multiple malignancies and TP53 gene mutation. [3] This case report comes close to being labeled as LFS.…”

Section: Introductionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

A case of synchronous malignancy with novel missense mutation in a child: Is this Li-Fraumeni syndrome or a novel case masquerading as Li-Fraumeni syndrome??

Raj

Redkar

Tewari

et al. 2020

Indian Journal of Medical and Paediatric Oncology

View full text Add to dashboard Cite

show abstract

“…Since gain-of-function mutations of p53 were reported to be stable for IHC [24][25][26], our data suggest that this new p53 mutation is not a gain-of-function mutation. Given that p53 gene mutation has a strong correlation with the diagnosis of infant ACC [19,27], genetic testing for p53 status was performed on the patient and his parents with their agreements. We found a heterozygous insertion of c.801dupG that caused a p.Asn268Glufs � 4 in the p53 gene in this patient and his mother, suggesting that this patient inherited the mutation from his healthy mother ( Fig 1D).…”

Section: P53 Asn268glufs � 4 Mutation Was Found In a Lfs Patientmentioning

confidence: 99%

“…In the present study, we generated iPS cells from the peripheral blood of a male infant with LFS; the patient has a p53 heterozygous mutation inherited from his mother (22 years old) [19]. The p53 mutation facilitates the proliferation of tumor cells by inhibiting apoptosis and promoting cell division.…”

Section: Introductionmentioning

confidence: 99%

The function of a heterozygous p53 mutation in a Li-Fraumeni syndrome patient

Tang

et al. 2020

PLoS ONE

Self Cite

View full text Add to dashboard Cite

p53 is one of the most extensively studied proteins in cancer research. Mutations in p53 generally abolish normal p53 function, and some mutants can gain new oncogenic functions. However, the mechanisms underlying p53 mutation-driven cancer remains to be elucidated. Our study investigated the function of a heterozygous p53 mutation (p. Asn268Glufs*4) in a Li-Fraumeni syndrome (LFS) patient. We used episomal technology to perform somatic reprogramming, and used molecular and cell biology methods to determine the p53 mutation levels in patient-originated induced pluripotent stem (iPS) cells at the RNA and protein levels. We found that p53 protein expression was not increased in this patient's somatic cells compared with those of a healthy control. p53 mutation facilitates the proliferation of tumor cells by inhibiting apoptosis and promoting cell division. It can inhibit the efficiency of somatic reprogramming by inhibiting OCT4 expression during reprogramming stage. Moreover, not all p53 mutant iPS cell lines have mutant p53 RNA sequences. A small percentage of mutant p53 mRNA is present in the somatic cells from the patient and his mother. In summary, this p53 mutation can promote tumor cell proliferation, inhibit somatic reprogramming, and exhibit random p53 allelic expression of heterozygous mutations in the patient and iPS cells which may be one of the reasons why the people with p53 mutations develop cancer at random. This finding suggested that mutant p53 allelic expression should be added to the risk forecasting of cancer.

show abstract

Molecular genotyping of adrenocortical carcinoma: a systematic analysis of published literature 2019–2021

Grisanti

Cosentini

Sigala

et al. 2021

Current Opinion in Oncology

View full text Add to dashboard Cite

Purpose of review comprehensive molecular characterization of adrenocortical carcinoma (ACC) through next-generation sequencing and bioinformatics analyses is expanding the number of targets with potential prognostic and therapeutic value. We performed a critical review of recent published literature on genotyping of ACC.Recent findings 423 studies were published between 2019 and 2021. After manual curation we summarized selected evidence in two thematic areas: germline deoxyribonucleic acid (DNA) variations, genomic alterations and prognosis. Summarythe evolving genomic landscape of ACC requires target validation in terms of prognostic and predictive value within scientific consortia. Although the existing multiple driver genes are difficult targets in the perspective of precision oncology, alterations in DNA damage repair genes or in promoter hypermethylation could open new venues for repurposing of existing drugs in ACC.

show abstract

Composite Adrenocortical Carcinoma and Neuroblastoma in an Infant With a TP53 Germline Mutation: A Case Report and Literature Review

Cited by 4 publications

References 20 publications

A case of synchronous malignancy with novel missense mutation in a child: Is this Li-Fraumeni syndrome or a novel case masquerading as Li-Fraumeni syndrome??

A case of synchronous malignancy with novel missense mutation in a child: Is this Li-Fraumeni syndrome or a novel case masquerading as Li-Fraumeni syndrome??

The function of a heterozygous p53 mutation in a Li-Fraumeni syndrome patient

Molecular genotyping of adrenocortical carcinoma: a systematic analysis of published literature 2019–2021

Contact Info

Product

Resources

About