Pediatric cancer and Li-Fraumeni/Li-Fraumeni-like syndromes: a review for the pediatrician

Giacomazzi, Cristina Rossi; Giacomazzi, Juliana; Netto, Cristina Brinckmann Oliveira; Santos-Silva, Patricia; Selistre, Simone Geiger de Almeida; Maia, Ana Luiza Silva; Oliveira, Viviane Ziebell de; Camey, Suzi Alves; Goldim, José Roberto; Ashton‐Prolla, Patrícia

doi:10.1590/1806-9282.61.03.282

Cited by 23 publications

(24 citation statements)

References 40 publications

(44 reference statements)

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“… 23 Another concern is the risk of overestimating the clinical implications of a P/LP result in a low- to moderate-risk gene. 24 A further criticism is the proportionate increase in the number of VUS for which management is unclear. Finally, multi-gene panels can require more extensive pre-test genetic counseling.…”

Section: Discussionmentioning

confidence: 99%

Expanded Gene Panel Use for Women With Breast Cancer: Identification and Intervention Beyond Breast Cancer Risk

et al. 2017

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BackgroundClinicians ordering multi-gene next-generation sequencing panels for hereditary breast cancer risk have a variety of test panel options. Many panels include lesser known breast cancer genes or genes associated with other cancers. The authors hypothesized that using broader gene panels increases the identification of clinically significant findings, some relevant and others incidental to the testing indication. They examined clinician ordering patterns and compared the yield of pathogenic or likely pathogenic (P/LP) variants in non-BRCA genes of female breast cancer patients.MethodsThis study analyzed de-identified personal and family histories in 1085 breast cancer cases with P/LP multi-gene panel findings in non-BRCA cancer genes and sorted them into three groups by the panel used for testing: group A (breast cancer genes only), group B (commonly assessed cancers: breast, gynecologic, and gastrointestinal), and group C (a more expanded set of tumors). The frequency of P/LP variants in genes with established management guidelines was compared and evaluated for consistency with personal and family histories.ResultsThis study identified 1131 P/LP variants and compared variants in clinically actionable genes for breast and non-breast cancers. Overall, 91.5% of these variants were in genes with management guidelines. Nearly 12% were unrelated to personal or family history.ConclusionBroader panels were used for 85.6% of our cohort (groups B and C). Although pathogenic variants in non-BRCA genes are reportedly rare, the study found that most were in clinically actionable genes. Expanded panel testing improved the identification of hereditary cancer risk. Small, breast-limited panels may miss clinically relevant findings in genes associated with other heritable cancers.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-017-5963-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Expanded Gene Panel Use for Women With Breast Cancer: Identification and Intervention Beyond Breast Cancer Risk

et al. 2017

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“…This syndrome differs from other hereditary cancer syndromes because it is not related to a specific type of cancer, but to a broad spectrum of tumors. 23 Syndrome variants include LFS1, LFS2 and LFS-like (LFSL). 21 In the South and Southeast regions of Brazil, there is a high frequency of Li-Fraumeni and Li-Fraumeni-like syndromes, because most of the population in these areas is of European origin.…”

Section: Discussionmentioning

confidence: 99%

Metachronic Breast and Cerebellar Neoplasm in a Young Patient

Nascimento

Haro

Sá

et al. 2020

Rev Bras Ginecol Obstet

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Several factors trigger the development of genetic mutations that are responsible for causing a neoplasm. Medulloblastoma is a malignant and invasive cerebellar neoplasm, that affects children and young adults. Mucinous carcinoma is a special type of breast cancer. Being a special atypical subtype of invasive carcinoma, it most frequently affects women of advanced age and represents 1 to 7% of all breast cancers. The reported case aims to show the rarity of the occurrence of desmoplastic medulloblastoma and mammary mucinous carcinoma in a young patient in a short period of time, in different sites, without direct anatomical attachment and without occurrence of metastasis. Initially, this patient had a desmoplastic medulloblastoma and was treated with lumpectomy and radiotherapy. After 13 months, the patient was diagnosed with a mucinous breast carcinoma, underwent mastectomy, adjuvant chemotherapy and is currently undergoing endocrinotherapy. We conclude, based on the metachronous characteristic of the neoplasia and clinical characteristics, that the patient is likely to have Li-Fraumeni syndrome, an autosomal dominant disease with mutation of the TP53 gene, which is the the main involved. Because the patient does not present all the characteristics of the phenotype of the syndrome, she can thus be classified as having Li-Fraumeni variant or Li-Fraumeni-like syndrome.

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“…LFS in children without any clinical symptoms of cancer, regular blood tests and ultrasonography (every 4 mo) are recommended for early detection of malignant tumors ( 23 ). Although our patient was already diagnosed with ACC, there is a need for careful and regular follow-up, in accordance with the course of childhood LFS, for earlier detection of ACC relapse and other malignant diseases because of the presence of a higher Weiss’s score and a TP53 gene mutation.…”

Section: Discussionmentioning

confidence: 99%

Adrenocortical carcinoma characterized by gynecomastia: A case report

Takeuchi

Yoto

Ishii

et al. 2018

Clin Pediatr Endocrinol

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Abstract.We present a 4-yr-old boy with adrenocortical carcinoma (ACC), diagnosed due to the appearance of gynecomastia as the presenting symptom. Six months prior to admission, an acute growth spurt along with the development of bilateral breast swelling was observed. He did not present any features of virilization, including enlargement of the testes, increase in testis volume, and penis size. Laboratory investigations showed gonadotropin-independent hypergonadism, with low LH/ FSH levels and elevated estradiol/testosterone levels. Abdominal computed tomography revealed a large heterogeneous mass adjacent to the right kidney and below the liver. Pathological investigations of the biopsy specimen demonstrated that the tumor was an ACC. Pre- and post-operative combination chemotherapy with mitotane was administered and surgical resection was carried out. Post-surgery, the elevated estradiol/testosterone concentrations reverted to within the reference range. Urinary steroid profile and tissue concentration analysis of estradiol and testosterone indicated the presence of estrogen in the ACC tissue. An investigation for TP53 gene aberrations revealed the presence of a germline point mutation in exon 4 (c.215C>G (p.Pro72Arg)). In ACC, the most common symptom is virilization, and feminization, characterized by gynecomastia, is very rare. However, a diagnostic possibility of ACC should be considered when we encounter patients who have developed gynecomastia without the influence of causative factors such as obesity or puberty, and do not present with the typical signs of virilization.

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Pediatric cancer and Li-Fraumeni/Li-Fraumeni-like syndromes: a review for the pediatrician

Cited by 23 publications

References 40 publications

Expanded Gene Panel Use for Women With Breast Cancer: Identification and Intervention Beyond Breast Cancer Risk

Expanded Gene Panel Use for Women With Breast Cancer: Identification and Intervention Beyond Breast Cancer Risk

Metachronic Breast and Cerebellar Neoplasm in a Young Patient

Adrenocortical carcinoma characterized by gynecomastia: A case report

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