Whole-Exome Sequencing Studies of Parathyroid Carcinomas Reveal Novel<i>PRUNE2</i>Mutations, Distinctive Mutational Spectra Related to APOBEC-Catalyzed DNA Mutagenesis and Mutational Enrichment in Kinases Associated With Cell Migration and Invasion

Yu, Willie; McPherson, John R.; Stevenson, Mark; Eijk, Ronald van; Heng, Hong Lee; Newey, Paul; Gan, Anna; Ruano, Dina; Huang, Dachuan; Poon, Song Ling; Ong, Choon Kiat; Wezel, Tom van; Cavaco, Branca; Rozen, Steve; Tan, Patrick; Teh, Bin Tean; Thakker, Rajesh V.; Morreau, Hans

doi:10.1210/jc.2014-3238

Cited by 91 publications

(109 citation statements)

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“…Although we could not exclude the possibility of metastatic sarcoma in the right ovary completely, we diagnosed an ovarian sarcoma on the basis of clinicopathological findings. We identified a nonsense mutation in PRUNE2 that was reported to be a potentially oncogenic30 but not therapeutically targetable mutated genes at that time. No somatic mutation of cancer‐associated genes frequently mutated in epithelial ovarian cancer—such as TP53, 31 KRAS, 32 PIK3CA ,33 and ARID1A 34—was detected.…”

Section: Discussionmentioning

confidence: 99%

Novel MXD4–NUTM1 fusion transcript identified in primary ovarian undifferentiated small round cell sarcoma

Tamura

Nakaoka

Yoshihara

et al. 2018

Genes Chromosomes & Cancer

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Primary ovarian sarcomas are extremely rare tumors, and their genomic and transcriptomic alterations remain to be elucidated. We performed whole exome sequencing of primary tumor and matched normal blood samples derived from one patient with ovarian undifferentiated small round cell sarcoma. We identified 8 nonsynonymous somatic mutations, and all mutations were missense or nonsense changes. Next, we performed RNA sequencing of the tumor sample and identified two in‐frame fusion transcripts: MXD4–NUTM1 and ARL6–POT1. Most NUTM1 exons were retained in the MXD4–NUTM1 fusion transcript, and we confirmed an increase in NUTM1 mRNA and protein expression in tumor tissue. Further genomic and transcriptomic analyses might lead to the development of new therapeutic strategies based on the molecular characteristics of ovarian undifferentiated small round cell sarcoma.

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Section: Discussionmentioning

confidence: 99%

Novel MXD4–NUTM1 fusion transcript identified in primary ovarian undifferentiated small round cell sarcoma

Tamura

Nakaoka

Yoshihara

et al. 2018

Genes Chromosomes & Cancer

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“…PRUNE2 has recently been identified as a likely tumor suppressor gene subject to recurrent mutation in parathyroid carcinoma [41,48] . Whole exome sequencing revealed one parathyroid carcinoma with a germline missense PRUNE2 mutation accompanied by allelic loss [48] and two carcinomas harboring biallelic, somatic nonsense mutations [41,48] .…”

Section: Prune2mentioning

confidence: 99%

“…Whole exome sequencing revealed one parathyroid carcinoma with a germline missense PRUNE2 mutation accompanied by allelic loss [48] and two carcinomas harboring biallelic, somatic nonsense mutations [41,48] . Sanger sequencing, limited to exon 8 of PRUNE2, uncovered two additional somatic missense mutations.…”

Section: Prune2mentioning

confidence: 99%

“…. Preferential amplification of mutant CDC73 alleles has been reported, which could account, at least in part, for observed alleic gain of chromosome 1q [48] . Whole genome/exome next-generation sequence analyses have identified a number of genes that may be important to the pathogenesis of parathyroid cancer and merit further study.…”

Section: Additional Genetic and Genomic Considerationsmentioning

confidence: 99%

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Parathyroid carcinoma

Costa-Guda¹

2018

JTGG

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Parathyroid carcinoma is a rare but clinically-aggressive tumor. While most cases are sporadic, parathyroid cancer is overrepresented in hyperparathyroidism-jaw tumor syndrome, or rarely other heritable syndromes. Evidence suggests that sporadic parathyroid carcinomas rarely, if ever, evolve through an identifiable benign tumor intermediate. A few genes have been directly implicated in the pathogenesis of sporadic parathyroid cancer; somatic (and less common germline) mutations in the CDC73 tumor suppressor gene are the most frequent finding and the only firmly established molecular drivers of parathyroid cancer. Alterations in other important human cancer genes, including CCND1 /cyclin D1, PIK3CA , MTOR and PRUNE2 have also been described in parathyroid cancer, however their abilities to drive malignant parathyroid tumorigenesis remains to be demonstrated experimentally.

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“…К другим генам-кандидатам, принимающим участие в патогенезе карцином ОЩЖ, отно-сят APC, CDKIs, PTEN, Rb1 и др. [2].…”

Section: Introductionunclassified

Atypical parathyroid adenoma with clinically aggressive course of hyperparathyroidism: clinical case report

et al. 2018

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Первичный гиперпаратиреоз занимает третье место по распространенности среди эндокринных заболеваний после сахарного диабета и патологии щитовидной железы, его частота во взрослой популяции составляет в среднем 1-2%. Наиболее часто при первичном гиперпаратиреозе выявляется солитарная аденома около-щитовидной железы (ОЩЖ) -80-85% случаев, реже гиперплазия и множественное поражение (до 15%), рак ОЩЖ встречается примерно в 1% наблюдений. Среди аденом ОЩЖ отдельно выделяют группу клинически агрессивных аденом, ассоциированных с более тяжелым течением заболевания, выраженной гиперкальциемией и неуточненным злокачественным потенциалом. В настоящее время нет четких критериев, которые помогли бы на дооперационном этапе дифференцировать атипическую аденому от карциномы и от "классической" аденомы. На сегодняшний день не существует критериев, позволивших бы на дооперационном этапе отличить атипическую аденому от типичной или рака ОЩЖ. Мы представляем случай 61-летней пациентки с клинически агрессивным течением первичного гиперпаратиреоза и выраженными метаболическими нарушениями структуры костной ткани очагового и диффузно-очагового характера вследствие атипической аденомы ОЩЖ. Ключевые слова: первичный гиперпаратиреоз, атипическая аденома околощитовидной железы, фиброзно-кистозный остеит, рак околощитовидных желез, остеосцинтиграфия, радионуклидная диаг ностика.Primary hyperparathyroidism is common clinical endocrine disorder with a prevalence between 1-2%. Solitary parathyroid adenomas account from 80 to 85% of cases of PHPT, hyperplasia and multiple adenomas is up to 15%, parathyroid carcinoma is a very rare cause of PHPT, accounting for about a 1% of cases. Clinically aggressive and atypical adenomas should be separately noted because of severe clinical course and life-threatening hypercalcemia, high morbidity and mortality, unknown malignant potential. No definite criteria are considered to be present to distinguish preoperatively atypical adenoma from parathyroid typical adenoma or carcinoma. The clinical course of the disease remains the only tool that allows to suspect an aggressive tumor on the preoperative stage. We present the clinical case of a 61-year-old female patient with a clinically "aggressive" course of PHPT and severe metabolic disturbances of bone tissue due to the atypical adenoma of the parathyroid gland.Key words: primary hyperparathyroidism, atypical parathyroid adenoma, cancer of the parathyroid glands, osteitis fibrosa cystica, osteoscintigraphy, radionuclide diagnostics.The article can used under the CC BY-NC-ND 4.0 license. Статья может быть использована на условиях международной лицензии CC BY-NC-ND 4.0.

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Whole-Exome Sequencing Studies of Parathyroid Carcinomas Reveal NovelPRUNE2Mutations, Distinctive Mutational Spectra Related to APOBEC-Catalyzed DNA Mutagenesis and Mutational Enrichment in Kinases Associated With Cell Migration and Invasion

Abstract: This study outlines the genetic landscape of PC and attempts to characterize the mutational processes shaping the PC genome.

Cited by 91 publications

References 17 publications

Novel MXD4–NUTM1 fusion transcript identified in primary ovarian undifferentiated small round cell sarcoma

Novel MXD4–NUTM1 fusion transcript identified in primary ovarian undifferentiated small round cell sarcoma

Parathyroid carcinoma

Atypical parathyroid adenoma with clinically aggressive course of hyperparathyroidism: clinical case report

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