Identification and characterization of a novel germline <i>p53</i> mutation in a patient with glioblastoma and colon cancer

Yamada, Hidetaka; Shinmura, Kazuya; Yamamura, Yuichi; Kurachi, Kiyotaka; Nakamura, Takamitsu; Tsuneyoshi, Toshihiro; Yokota, Naoki; Maekawa, Masato; Sugimura, Haruhiko

doi:10.1002/ijc.24432

Cited by 16 publications

(12 citation statements)

References 15 publications

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“…However, in the present case and in other case reports of LFS patients (10,13), a large part of the normal mucosa was negative on immunohistochemical staining for p53. Furthermore, in many cases of TP53 germline mutation, loss of function or deletion of the wild type allele is needed for phenotypic manifestation and the initiation of tumor development (14).…”

Section: Discussioncontrasting

confidence: 68%

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The Features of Colorectal Tumors in a Patient with Li-Fraumeni Syndrome

et al. 2017

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A young woman with Li-Fraumeni syndrome (LFS) was referred to our hospital. On examination, multiple flat neoplasms were detected in addition to semi-pedunculated polyps. Restorative proctocolectomy was performed; one submucosal invasive cancer, two mucosal cancers, and several adenomas with high-grade dysplasia were detected. On immunohistochemical staining with p53, every part of all neoplasms, even the small adenomas, showed strong positive staining. Multiple flat neoplasms may be characteristic of patients with LFS and may have a much higher risk of rapid progression to invasive carcinomas than sporadic neoplasms. Thus, careful and frequent colonoscopy surveillance may be needed for patients with LFS.

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Section: Discussioncontrasting

confidence: 68%

“…Some case reports have been published on LFS patients with colon cancer (9,10), but no detailed data on the shape or size or concomitant colon neoplasms have been collected. Miyaki et al reported a case of a patient with a germ line TP53 mutation who had advanced colon cancer with multiple early adenocarcinomas and adenoma (11).…”

Section: Discussionmentioning

confidence: 99%

The Features of Colorectal Tumors in a Patient with Li-Fraumeni Syndrome

et al. 2017

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“…A functional assay may be useful for determining the clinical significance of novel missense mutations [4]. It has been indicated that approximately 70% of LFS patients and 8–22% of patients with LFL syndrome have detectable p53 mutations [5].…”

Section: Introductionmentioning

confidence: 99%

Li-Fraumeni syndrome with simultaneous osteosarcoma and liver cancer: Increased expression of a CD44 variant isoform after chemotherapy

et al. 2012

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BackgroundLi-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome that is commonly associated with a germline mutation in the tumor suppressor gene p53. Loss of p53 results in increased expression of CD44, a cancer stem cell (CSC) marker, which is involved in the scavenging of reactive oxygen species (ROS). Here, we report a change in the expression of a CD44 variant isoform (CD44v8-10) in an 8-year-old female LFS patient with osteosarcoma and atypical liver cancer after chemotherapy.Case presentationThe patient visited a clinic with a chief complaint of chronic pain in a bruise on her right knee. Magnetic resonance imaging (MRI) raised the possibility of a bone malignancy. Biochemical testing also revealed significantly elevated levels of AFP, which strongly suggested the existence of a primary malignancy in the liver. MRI imaging showed the simultaneous development of osteosarcoma and liver cancer, both of which were confirmed upon biopsy. Combined therapy with surgical resection after chemotherapy was successful in this patient. Regardless of the absence of a familial history of hereditary cancer, a germline mutation in p53 was identified (a missense mutation defined as c.722 C>T, p.Ser241Phe). To better understand the cancer progression and response to treatment, immunohistochemical (IHC) analysis of biopsy specimens obtained before and after chemotherapy was performed using a specific antibody against CD44v8-10.ConclusionThis case demonstrates the ectopic up-regulation of CD44v8-10 in a biopsy sample obtained after cytotoxic chemotherapy, which confers high levels of oxidative stress on cancer cells. Because the alternative splicing of CD44 is tightly regulated epigenetically, it is possible that micro-environmental stress resulting from chemotherapy caused the ectopic induction of CD44v8-10 in vivo.

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“…Recently, testing recommendations have been broadened to include women with early-onset breast cancer in the absence of family history or BRCA1/ BRCA2 mutations (McCuaig et al 2012), as they would be suspected of carrying de novo TP53 germline mutations (Gonzalez et al 2009). In addition, germline TP53 mutations have now been uncovered in patients who did not fulfill the clinical criteria for LFS testing, but presented with rare pediatric cancers including hypodiploid acute lymphoblastic leukemia (Holmfeldt et al 2013), melanoma (Lu et al 2015), gastric adenocarcinoma (Chang et al 2013), early-onset colorectal cancer (Yurgelun et al 2015), early-onset osteosarcoma (Mirabello et al 2015), or multiple early-onset malignancies (Yamada et al 2009;Chak et al 2015). The wide application of NGS technologies will undoubtedly lead to more such findings and require continued reassessment of the role of TP53 germline variants in cancer predisposition and the need for intense surveillance of mutation carriers and their families (Villani et al 2011).…”

Section: Germline Tp53 Mutations and Cancer Predispositionmentioning

confidence: 99%

Clinical Outcomes of TP53 Mutations in Cancers

Robles

Jen

Harris

2016

Cold Spring Harb Perspect Med

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High-throughput sequencing of cancer genomes is increasingly becoming an essential tool of clinical oncology that facilitates target identification and targeted therapy within the context of precision medicine. The cumulative profiles of somatic mutations in cancer yielded by comprehensive molecular studies also constitute a fingerprint of historical exposures to exogenous and endogenous mutagens, providing insight into cancer evolution and etiology. Mutational signatures that were first established by inspection of the TP53 gene somatic landscape have now been confirmed and expanded by comprehensive sequencing studies. Further, the degree of granularity achieved by deep sequencing allows detection of low-abundance mutations with clinical relevance. In tumors, they represent the emergence of small aggressive clones; in normal tissues, they signal a mutagenic exposure related to cancer risk; and, in blood, they may soon become effective surveillance tools for diagnostic purposes and for monitoring of cancer prognosis and recurrence.

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Identification and characterization of a novel germline p53 mutation in a patient with glioblastoma and colon cancer

Cited by 16 publications

References 15 publications

The Features of Colorectal Tumors in a Patient with Li-Fraumeni Syndrome

The Features of Colorectal Tumors in a Patient with Li-Fraumeni Syndrome

Li-Fraumeni syndrome with simultaneous osteosarcoma and liver cancer: Increased expression of a CD44 variant isoform after chemotherapy

Clinical Outcomes of TP53 Mutations in Cancers

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