Tricuspid mass-curious case of Li-Fraumeni syndrome: A case report.

BACKGROUND: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer-predisposing syndrome, which can manifest as a polymorphic spectrum of malignancies. LFS is associated with an early onset in life, with the majority of cases occurring prior to the age of 46. Notwithstanding the infrequency of primary cardiac tumors, it behooves clinicians to remain vigilant in considering the differential diagnosis of such tumors in LFS patients who present with a cardiac mass. This is due to the markedly elevated risk for malignancy in this particular population, far surpassing that of the general populace. CASE SUMMARY: Herein, we present a case of a 30-year-old female with LFS who was found to have a tricuspid valve leaflet mass. CONCLUSION: This case exemplifies valuable learning points in the diagnostic approach for this exceptionally rare patient population.

Pediatric-type high-grade gliomas with PDGFRA amplification in adult patients with Li-Fraumeni syndrome: clinical and molecular characterization of three cases.

Li-Fraumeni syndrome (LFS) is an autosomal dominant tumor predisposition syndrome caused by heterozygous germline mutations or deletions in the TP53 tumor suppressor gene. Central nervous system tumors, such as choroid plexus tumors, medulloblastomas, and diffuse gliomas, are frequently found in patients with LFS. Although molecular profiles of diffuse gliomas that develop in pediatric patients with LFS have been elucidated, those in adults are limited. Recently, diffuse gliomas have been divided into pediatric- and adult-type gliomas, based on their distinct molecular profiles. In the present study, we investigated the molecular profiles of high-grade gliomas in three adults with LFS. These tumors revealed characteristic histopathological findings of high-grade glioma or glioblastoma and harbored wild-type IDH1/2 according to whole exome sequencing (WES). However, these tumors did not exhibit the key molecular alterations of glioblastoma, IDH-wildtype such as TERT promoter mutation, EGFR amplification, or chromosome 7 gain and 10 loss. Although WES revealed no other characteristic gene mutations or copy number alterations in high-grade gliomas, such as those in histone H3 genes, PDGFRA amplification was found in all three cases together with uniparental disomy of chromosome 17p, where the TP53 gene is located. DNA methylation analyses revealed that all tumors exhibited DNA methylation profiles similar to those of pediatric-type high-grade glioma H3-wildtype and IDH-wildtype (pHGG H3-/IDH-wt), RTK1 subtype. These data suggest that high-grade gliomas developed in adult patients with LFS may be involved in pHGG H3-/IDH-wt. PDGFRA and homozygous alterations in TP53 may play pivotal roles in the development of this type of glioma in adult patients with LFS.

Case report: Therapy-related myeloid neoplasms in three pediatric cases with medulloblastoma.

Introduction: Medulloblastoma is the most common malignant brain tumor in children, often requiring intensive multimodal therapy, including chemotherapy with alkylating agents. However, therapy-related complications, such as therapy-related myeloid neoplasms (t-MNs), can arise, particularly in patients with genetic predisposition syndromes. This case report presents three pediatric cases of medulloblastoma with subsequent development of t-MNs, highlighting the potential role of genetic predisposition and the importance of surveillance for hematological abnormalities in long-term survivors. Case presentation: We describe three cases of pediatric medulloblastoma who developed t-MNs after receiving chemotherapy, including alkylating agents. Two of the patients had underlying genetic predisposition syndromes (TP53 pathologic variants). The latency period between initial diagnosis of medulloblastoma and the development of secondary cancer varied among the cases, ranging from 17 to 65 months. The three cases eventually succumbed from secondary malignancy, therapy-related complications and progression of primary disease, respectively. Conclusions: This report highlights the potential association between genetic predisposition syndromes and the development of therapy-related myeloid neoplasms in pediatric medulloblastoma survivors. It underscores the importance of surveillance for hematological abnormalities among such patients.

Whole-Body MRI Screening for Carriers of Germline TP53 Mutations-A Systematic Review and Meta-Analysis.

PURPOSE: This systematic review evaluated whole-body MRI (WB-MRI) as a cancer screening tool for individuals carrying germline TP53 mutations, a population known to be at a significantly elevated risk of malignancy. The primary objective is to assess the diagnostic performance of WB-MRI in detecting cancer in this cohort. METHODS: PubMed, MEDLINE, EMBASE and the Cochrane Central Registry of Controlled Trials were searched until 18 August 2023. Eligible studies were selected based on predefined inclusion criteria. The data extracted included information on study characteristics, patient demographics, and the WB-MRI diagnostic performance. RESULTS: This systematic review identified eight eligible studies, comprising 506 TP53 mutation carriers. The mean age was 34.6 ± 16.3 (range 1-74) years. In total, 321/506 (63.4%) of the patients were female and 185/506 (36.6%) were male. In addition, 267/506 (52.8%) had a previous oncological diagnosis. Thirty-six new cancers were diagnosed with WB-MRI (36/506 (7.1%)). The overall pooled proportion of cancer detected on MRI was 7% (95% confidence interval 5-10). In total, 44 new lesions were picked up, as multiple lesions were found in some patients. CONCLUSION: WB-MRI is an effective cancer screening tool for TP53 mutation carriers. While these findings suggest the potential for WB-MRI to contribute to early cancer detection in this high-risk population, further research and the standardisation of protocols internationally are warranted to optimise its clinical utility.

Gender-Affirming Care in a Transgender Young Woman With Li-Fraumeni Syndrome: A Case Report.

The number of youths who identify with a gender different from their sex designated at birth is increasing. Youth account for about 4% of all cancer diagnoses in the United States. Some youths may want gender-affirming medical treatment, such as puberty blockers and/or hormone therapy, which may exacerbate cancer and/or increase cancer development risk. No studies assess the impact of estrogen-based treatment in gender-diverse youth with a history of Li-Fraumeni syndrome. This case report will discuss gender-affirming care and shared decision-making in a youth with a history of Li-Fraumeni syndrome and increased risk for breast cancer.

Risk factors for glioblastoma are shared by other brain tumor types.

The reported risk factors for glioblastoma (GBM), i.e., ionizing radiation, Li-Fraumeni syndrome, Neurofibromatosis I, and Turcot syndrome, also increase the risk of other brain tumor types. Risk factors for human GBM are associated with different oncogenic mutation profiles. Pedigreed domestic dogs with a shorter nose and flatter face (brachycephalic dogs) display relatively high rates of glioma formation. The genetic profiles of canine gliomas are also idiosyncratic. The association of putatively different mutational patterns in humans and canines with GBM suggests that different oncogenic pathways can result in GBM formation. Strong epidemiological evidence for an association between exposure to chemical carcinogens and an increased risk for development of GBM is currently lacking. Ionizing radiation induces point mutations, frameshift mutations, double-strand breaks, and chromosomal insertions or deletions. Mutational profiles associated with chemical exposures overlap with the broad mutational patterns seen with ionizing radiation. Weak statistical associations between chemical exposures and GBM reported in epidemiology studies are biologically plausible. Molecular approaches comparing reproducible patterns seen in spontaneous GBM with analogous patterns found in GBMs resected from patients with known significant exposures to potentially carcinogenic chemicals can address difficulties presented by traditional exposure assessment.

Cancer Precision-Prevention trial of Metformin in adults with Li Fraumeni syndrome (MILI) undergoing yearly MRI surveillance: a randomised controlled trial protocol.

BACKGROUND: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disease caused by inherited or de novo germline pathogenic variants in TP53. Individuals with LFS have a 70-100% lifetime risk of developing cancer. The current standard of care involves annual surveillance with whole-body and brain MRI (WB-MRI) and clinical review; however, there are no chemoprevention agents licensed for individuals with LFS. Preclinical studies in LFS murine models show that the anti-diabetic drug metformin is chemopreventive and, in a pilot intervention trial, short-term use of metformin was well-tolerated in adults with LFS. However, metformin's mechanism of anticancer activity in this context is unclear. METHODS: Metformin in adults with Li-Fraumeni syndrome (MILI) is a Precision-Prevention phase II open-labelled unblinded randomised clinical trial in which 224 adults aged ≥ 16 years with LFS are randomised 1:1 to oral metformin (up to 2 mg daily) plus annual MRI surveillance or annual MRI surveillance alone for up to 5 years. The primary endpoint is to compare cumulative cancer-free survival up to 5 years (60 months) from randomisation between the intervention (metformin) and control (no metformin) arms. Secondary endpoints include a comparison of cumulative tumour-free survival at 5 years, overall survival at 5 years and clinical characteristics of emerging cancers between trial arms. Safety, toxicity and acceptability of metformin; impact of metformin on quality of life; and impact of baseline lifestyle risk factors on cancer incidence will be assessed. Exploratory end-points will evaluate the mechanism of action of metformin as a cancer preventative, identify biomarkers of response or carcinogenesis and assess WB-MRI performance as a diagnostic tool for detecting cancers in participants with LFS by assessing yield and diagnostic accuracy of WB-MRI. DISCUSSION: Alongside a parallel MILI study being conducted by collaborators at the National Cancer Institute (NCI), MILI is the first prevention trial to be conducted in this high-risk group. The MILI study provides a unique opportunity to evaluate the efficacy of metformin as a chemopreventive alongside exploring its mechanism of anticancer action and the biological process of mutated P53-driven tumourigenesis. TRIAL REGISTRATION: ISRCTN16699730. Registered on 28 November 2022. URL: https://www.isrctn.com/ EudraCT/CTIS number 2022-000165-41.

Laser interstitial thermal therapy as a radiation-sparing approach for central nervous system tumors in children with cancer predisposition syndromes: report of a child with Li-Fraumeni syndrome. Illustrative case.

BACKGROUND: Ionizing radiation and alkylating chemotherapies increase secondary malignancy risk in patients with cancer predisposition syndromes (CPSs), such as Li-Fraumeni syndrome. Laser interstitial thermal therapy (LITT) is a minimally invasive ablation technique that has not been associated with mutagenic risks. We describe the case of a child with LFS and a history of treated choroid plexus carcinoma (CPC) who developed a second primary glial tumor that was safely treated with magnetic resonance imaging (MRI)-guided LITT. OBSERVATIONS: A 4-year-old male with left parietal World Health Organization grade III CPC associated with a TP53 germline mutation was evaluated. The patient underwent neoadjuvant platinum-based chemotherapy before near-total resection, followed by 131I-8H9 immunotherapy and 30 fractions of 54-Gy proton radiotherapy. He remained without evidence of disease for 2 years before developing a slow-growing mass adjacent to the left frontal ventricular horn. Stereotactic biopsy revealed a glial neoplasm. Given the nonsuperficial location and focality of the lesion, MRI-guided LITT was performed for ablative therapy. There were no complications, and 2 years of surveillance revealed continued retraction of the ablated tumor focus and no subsequent disease. LESSONS: Alternatives to mutagenic therapies for brain tumors should be explored for patients with CPS. LITT paired with imaging surveillance is a logical strategy to ensure durable outcomes and mitigate treatment-related secondary neoplasms.

Health-related quality of life and fear of progression in individuals with Li-Fraumeni syndrome.

Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome associated with a highly elevated lifetime cancer risk. This and the recommended intense surveillance program represent a large psychological burden on families. In order to develop targeted psychosocial interventions, we conducted a needs assessment. Adults (≥18 years) with LFS were included via regular hospital visits and online support groups and newsletters. Individuals filled out a questionnaire addressing among others: fear of progression (FoP-questionnaire, short-form), health-related quality of life (HRQoL, Short-Form Health Survey-12), distress (National Comprehensive Cancer Network distress thermometer), perceived cancer risk, and aspects of surveillance adherence. Collecting data over a 14-month period (March 2020 - June 2021), 70 adults were recruited (female = 58, 82.9%; mean age = 41.53 years). With mean mental component scores (MCS) of 42.28 (SD = 10.79), and physical component scores (PCS) of 48.83 (SD = 10.46), HRQoL was low in 34.8% (physical) and 59.4% (mental) of individuals when applying a mean cut-off of 45.4 (PCS) and 47.5 (MCS) to indicate poor HRQoL. High levels of FoP and distress were present in 68.6% and 69.1% of the participants, respectively. Performing a multiple linear regression on MCS and PCS, no sociodemographic variable was shown to be significant. FoP (ß = -0.33, p < 0.05) and distress (ß = -0.34, p < 0.05) were significantly associated with MCS. Individuals in our sample were burdened more than expected, with the majority reporting low levels of (mental) HRQoL, high distress, and FoP. Psychosocial support is necessary to help individuals with LFS (survivors as well as "previvors") increase their HRQoL, as it is crucial to survival.

Hematologic malignancies in Li-Fraumeni syndrome: A case report.

Li-Fraumeni syndrome (LFS) is a rare syndrome characterized by an increased lifetime risk of cancer development in multiple organ systems, typically caused by de novo or inherited germline pathogenic variants in the tumor suppressor TP53 gene. LFS is more classically associated with solid tumors; however, it is also associated with hematologic malignancies such as therapy-related acute myeloid leukemia (AML). We present the case of a female patient with a strong family and personal history of cancer who presented to our institution with therapy-related AML with next-generation sequencing showing a pathogenic TP53 mutation. She received several lines of systemic therapy and underwent stem cell transplant using her adult daughter as a haploidentical donor after achieving minimal residual disease (MRD). Her posttransplant bone marrow evaluations demonstrated persistence of the same pathogenic TP53 mutation despite ongoing clinical remission with full donor engraftment and negative MRD. Genetic testing was performed which confirmed the germline origin of the TP53 pathogenic variant in the patient. The patient's adult donor daughter was also identified to have the same pathogenic variant in TP53 consistent with LFS. The presented case highlights the need for increased awareness of LFS in the adult hematologic community, particularly for patients undergoing evaluation for stem cell transplant.

Li Fraumeni Syndrome predisposes to gastro-esophageal junction tumours.

Li-Fraumeni Syndrome (LFS), caused by germline pathogenic variants in TP53, predisposes to a wide range of young-onset malignancies, particularly sarcoma, breast and brain cancer. More recently, an increased risk of gastric adenocarcinoma has been recognised, although uptake of surveillance upper endoscopy is unclear. Our retrospective review of 65 patients with LFS, of whom 53.8% had undergone endoscopy, identified four patients (6.2%) with gastro-esophageal junction (GEJ) adenocarcinomas. Two cases were found on asymptomatic screening and were early stage. No cases had family history of gastrointestinal malignancy. Reviewing genomic data from The Cancer Genome Atlas Program, 76.4% of sporadic esophageal adenocarcinomas harboured somatic TP53 pathogenic variants, compared with 39.9% of non-cardia gastric cancers. This similar pattern observed in germline and sporadic cases warrants further investigation. We propose that upper endoscopy be recommended to all patients with LFS, with a focus on appropriate surveillance of the GEJ.

Li-Fraumeni Syndrome with Unusual Synchronous Malignancies: A Case Report.

Introduction: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disorder brought on by pathogenic mutations in the TP53 tumor suppressor gene. LFS is characterized by a high lifetime risk of developing various cancers at a relatively young age. Case Presentation: We are presenting a 48-year-old male with a diagnosis of LFS that was confirmed by a genetic test triggered by the patient's son's diagnosis of LFS and leukemia. The patient's main symptoms were abdominal pain and weight loss. The patient was diagnosed with two synchronous primary tumors: first, a metastatic gastric invasive adenocarcinoma that is microsatellite instability (MSI) -high; and second, a low grade (G1) (non-function) well-differentiated pancreatic neuroendocrine tumor. These cancers are not the usual type associated with LFS. After eight cycles of chemo-immunotherapy in the form of FOLFOX-Nivolumab, our radiological assessment showed significant response in the metastatic gastric adenocarcinoma and stable disease in pancreatic neuroendocrine tumor. The patient remains on single agent Nivolumab and has had stable disease for the last 12 months. Conclusion: Gastric cancer and neuroendocrine tumors are not usually associated with LFS. This case illustrates a rare clinical presentation of multiple malignancies in LFS patients.

Li-Fraumeni syndrome presenting with de novo TP53 mutation, severe phenotype and advanced paternal age: a case report.

BACKGROUND: Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer syndrome caused by pathogenic variants in the gene TP53. This gene codes for the P53 protein, a crucial player in genomic stability, which functions as a tumor suppressor gene. Individuals with LFS frequently develop multiple primary tumors at a young age, such as soft tissue sarcomas, breast cancer, and brain tumors. CASE PRESENTATION: A 38 years-old female with a history of femur osteosarcoma, ductal carcinoma of the breast, high-grade breast sarcoma, pleomorphic sarcoma of the left upper limb, infiltrating lobular carcinoma of the breast, gastric adenocarcinoma, leiomyosarcoma of the right upper limb, and high-grade pleomorphic renal sarcoma. Complete molecular sequencing of the TP53 gene showed c.586 C > T (p.R196X) in exon 6, which is a nonsense mutation that produces a shorter and malfunctioning P53. Family history includes advanced father's age at the time of conception (75 years), which has been associated with an increased risk of de novo germline mutations. The patient had seven paternal half-siblings with no cancer history. The patient received multiple treatments including surgery, systemic therapy, and radiotherapy, but died at the age of 38. CONCLUSIONS: Advanced paternal age is a risk factor to consider when hereditary cancer syndrome is suspected. Early detection of hereditary cancer syndromes and their multi-disciplinary surveillance and treatment is important to improve clinical outcomes for these patients. Further investigation of the relationship between the pathogenic variant of TP53 and its phenotype may guide the stratification of surveillance and treatment.

Epithelioid angiomyolipoma of the liver in a patient with Li-Fraumeni syndrome: a case report.

BACKGROUND: Epithelioid angiomyolipoma (EAML) is a rare variant of angiomyolipoma that predominantly consists of epithelioid cells and belongs to the perivascular epithelioid cell neoplasm (PEComa) family. The majority of EAMLs arise in the kidneys, and primary hepatic EAML appears to be much less common than renal EAML. Most PEComas arise sporadically, but may be associated with tuberous sclerosis complex (TSC), an autosomal dominant genetic disorder characterized by germline mutations in the TSC1 or TSC2 genes. However, PEComas have previously been reported in five patients with Li-Fraumeni syndrome (LFS), which is an inherited cancer susceptibility disorder resulting from germline mutations in the TP53 tumor suppressor gene. CASE PRESENTATION: We report a 49-year-old female patient with hepatic EAML and pancreatic cancer. Because she had previously been diagnosed with bilateral breast cancer at the age of 30, we performed a comprehensive genetic analysis to identify genetic alterations associated with any cancer predisposition syndrome. Whole-exome sequencing of a blood sample identified a heterozygous germline variant of TP53 (NM_000546.5):c.708C>A, and targeted next-generation sequencing of liver EAML and pancreatic cancer tissue samples demonstrated the same TP53 (NM_000546.5):c.708C>A variant in both. This, plus the patient's history of early-onset breast cancer, met the 2015 version of the Chompret criteria for diagnosis of LFS. CONCLUSIONS: There have been very few case reports regarding the presence of PEComa in LFS, and to the best of our knowledge, this is the first report of EAML of the liver in a patient with LFS.

Medical students' knowledge on cancer predisposition syndromes and attitude toward eHealth.

PURPOSE: Individuals with cancer predisposition syndromes (CPS) inherit elevated cancer risks. Medical supply gaps for people at risk of CPS cause insufficient outreach and miss potential benefits of individualized care strategies. Increased awareness of CPS and progress in the eHealth sector are untapped sources of health care improvement for affected individuals. METHODS AND RESULTS: This study addressed German-speaking medical students with an online questionnaire in respect to their knowledge of CPS, their medical education, and perspectives. The study population (n = 404) reported interest in and knowledge of CPS, supported by a satisfactory and sustainable education for their prospective patient care. The next generation of doctors would implement eHealth to improve medical services. Skepticism about digitization was claimed by students. They were especially concerned about deterioration in the physician-patient relationship, data abuse, dependence on technology, and incorrect diagnoses. CONCLUSION: Due to increasing diagnosing of CPS and deeper knowledge, this topic is essential for the curriculum in medical schools. In particular, care providers need know-how on identifying patients at risk for a CPS, certain diagnostic and therapeutic steps, surveillance and prophylactic strategies to improve patients' outcomes. Education in medical school as well as implemented eHealth seems to have potential to meet this demand in an upcoming era of personalized medicine. What does this study add to the clinical work. Medical teaching on cancer predisposition syndromes should be expanded to improve knowledge and individualized and personalized healthcare.

Genome-first approach of the prevalence and cancer phenotypes of pathogenic or likely pathogenic germline TP53 variants.

Pathogenic or likely pathogenic (P/LP) germline TP53 variants are the primary cause of Li-Fraumeni syndrome (LFS), a hereditary cancer predisposition disorder characterized by early-onset cancers. The population prevalence of P/LP germline TP53 variants is estimated to be approximately one in every 3,500 to 20,000 individuals. However, these estimates are likely impacted by ascertainment biases and lack of clinical and genetic data to account for potential confounding factors, such as clonal hematopoiesis. Genome-first approaches of cohorts linked to phenotype data can further refine these estimates by identifying individuals with variants of interest and then assessing their phenotypes. This study evaluated P/LP germline (variant allele fraction ≥30%) TP53 variants in three cohorts: UK Biobank (UKB, n = 200,590), Geisinger (n = 170,503), and Penn Medicine Biobank (PMBB, n = 43,731). A total of 109 individuals were identified with P/LP germline TP53 variants across the three databases. The TP53 p.R181H variant was the most frequently identified (9 of 109 individuals, 8%). A total of 110 cancers, including 47 hematologic cancers (47 of 110, 43%), were reported in 71 individuals. The prevalence of P/LP germline TP53 variants was conservatively estimated as 1:10,439 in UKB, 1:3,790 in Geisinger, and 1:2,983 in PMBB. These estimates were calculated after excluding related individuals and accounting for the potential impact of clonal hematopoiesis by excluding heterozygotes who ever developed a hematologic cancer. These varying estimates likely reflect intrinsic selection biases of each database, such as healthcare or population-based contexts. Prospective studies of diverse, young cohorts are required to better understand the population prevalence of germline TP53 variants and their associated cancer penetrance.

Clinical Features of Li-Fraumeni Syndrome in Korea.

PURPOSE: Li-Fraumeni syndrome (LFS) is a hereditary disorder caused by germline mutation in TP53. Owing to the rarity of LFS, data on its clinical features are limited. This study aimed to evaluate the clinical characteristics and prognosis of Korean patients with LFS. MATERIALS AND METHODS: Patients who underwent genetic counseling and confirmed with germline TP53 mutation in the National Cancer Center in Korea between 2011 and 2022 were retrospectively reviewed. Data on family history with pedigree, types of mutation, clinical features, and prognosis were collected. RESULTS: Fourteen patients with LFS were included in this study. The median age at diagnosis of the first tumor was 32 years. Missense and nonsense mutations were observed in 13 and one patients, respectively. The repeated mutations were p.Arg273His, p.Ala138Val, and pPro190Leu. The sister with breast cancer harbored the same mutation of p.Ala138Val. Seven patients had multiple primary cancers. Breast cancer was most frequently observed, and other types of tumor included sarcoma, thyroid cancer, pancreatic cancer, brain tumor, adrenocortical carcinoma, ovarian cancer, endometrial cancer, colon cancer, vaginal cancer, skin cancer, and leukemia. The median follow-up period was 51.5 months. Two and four patients showed local recurrence and distant metastasis, respectively. Two patients died of leukemia and pancreatic cancer 3 and 23 months after diagnosis, respectively. CONCLUSION: This study provides information on different characteristics of patients with LFS, including types of mutation, types of cancer, and prognostic outcomes. For more appropriate management of these patients, proper genetic screening and multidisciplinary discussion are required.

Functional pri-miR-34b/c rs4938723 and KRAS 3'UTR rs61764370 SNPs: Novel phenotype modifiers in Li-Fraumeni Syndrome?

PURPOSE: Li-Fraumeni Syndrome (LFS) is a rare cancer predisposing condition caused by germline pathogenic TP53 variants, in which core tumors comprise sarcomas, breast, brain and adrenocortical neoplasms. Clinical manifestations are highly variable in carriers of the Brazilian germline founder variant TP53 p.R337H, possibly due to the influence of modifier genes such as miRNA genes involved in the regulation of the p53 pathway. Herein, we investigated the potential phenotypic effects of two miRNA-related functional SNPs, pri-miR-34b/c rs4938723 and 3'UTR KRAS rs61764370, in a cohort of 273 LFS patients from Southern and Southeastern Brazil. METHODS: The genotyping of selected SNPs was performed by TaqMan® allelic discrimination and subsequently custom TaqMan® genotyping results were confirmed by Sanger sequencing in all SNP-positive LFS patients. RESULTS: Although the KRAS SNP showed no effect as a phenotype modulator, the rs4938723 CC genotype was significantly associated with development of LFS non-core tumors (first tumor diagnosis) in p.R337H carriers (p = 0.039). Non-core tumors were also more frequently diagnosed in carriers of germline TP53 DNA binding domain variants harboring the rs4938723 C variant allele. Previous studies described pri-miR-34b/c rs4938723 C as a risk allele for sporadic occurrence of thyroid and prostate cancers (non-core tumors of the LFS spectrum). CONCLUSION: With this study, we presented additional evidence about the importance of analyzing miRNA genes that could indirectly regulate p53 expression, and, therefore, may modulate the LFS phenotype, such as those of the miR-34 family.

Pleomorphic dermal sarcoma presenting in a child with Li-Fraumeni syndrome: A case report and review of the literature.

Pleomorphic dermal sarcoma (PDS) is an uncommon malignant soft-tissue tumor that occurs mostly in elderly patients, with only 5% of cases occurring in children. However, pediatric patients with Li-Fraumeni syndrome (LFS) can develop several types of cancer, particularly sarcomas. Here, we describe a young LFS patient who presented with early-onset PDS and review the literature.