ライフサイエンスコーパス: germline mutation

1 surveillance but were not known to harbor a germline mutation.

2 ning patients with a history suggestive of a germline mutation.

3 riampullary neoplasms also had a deleterious germline mutation.

4 atients with HGSC with either BRCA1 or BRCA2 germline mutation.

5 ukemia model evolving on the background of a germline mutation.

6 k of progression in a cohort without a known germline mutation.

7 disease through epigenetic modifications or germline mutations.

8 has potential for the targeted correction of germline mutations.

9 tive options offered to women with high-risk germline mutations.

10 irst human disease related to potential TET2 germline mutations.

11 ases, especially those caused by deleterious germline mutations.

12 , were investigated to identify predisposing germline mutations.

13 Two patients exhibited LZTR1 germline mutations.

14 rther increased by already present oncogenic germline mutations.

15 ions and in 0.4% of patients (1 of 223) with germline mutations.

16 age and maternal age in the genesis of human germline mutations.

17 nts with pancreatic cancer had a deleterious germline mutation, 31 (3.5%) of which affected known fam

18 d, including those with familial risk due to germline mutations, a history of pancreatitis, patients

19 Observations: BRCA1 and BRCA2 germline mutations account for up to 30% of inheritable

20 Adult germline mutation accumulation rates are established in

21 Our results demonstrate that rates of germline mutation accumulation vary among families with

22 Biallelic germline mutations affecting NTHL1 predispose carriers t

23 quencing to identify previously unrecognized germline mutations among these 345 individuals.

24 ases did not show a known correlation of the germline mutation and a known syndrome.

25 genetic diagnosis (the M+ group): 49 carried germline mutations and 3 carried somatic variants.

26 we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous

27 s been implied in studies describing de novo germline mutations and copy number variants.

28 rental radiation exposure is associated with germline mutations and genomic alterations in the offspr

29 of being transmitted to offspring as de novo germline mutations and, in principle, can provide insigh

30 Intratumoral genetic heterogeneity, germline mutations, and therapeutic actionability were a

31 Germline mutations are a driving force behind genome evo

32 , it has become increasingly recognized that germline mutations are common in many of these neoplasms

33 Cancers that arise from BRCA1 germline mutations are deficient for homologous recombin

34 In humans, most germline mutations are inherited from the father.

35 Few germline mutations are known to affect lung cancer risk.

36 In humans, most germline mutations are paternal in origin and numbers of

37 The clinical consequences of PMS2 germline mutations are poorly understood compared with o

38 The sources of human germline mutations are poorly understood.

39 xpressed deubiquitinase for histone H2A, but germline mutations are predominantly associated with uve

40 nd patients with DICER1 syndrome with DICER1 germline mutations are susceptible to childhood cancers.

41 Germline mutations are the source of evolution and contr

42 These data implicate this PARK2 germline mutation as a genetic susceptibility factor for

43 y outcome was identification of a pathogenic germline mutation associated with cancer predisposition.

44 h CRC at age younger than 50 years carries a germline mutation associated with cancer; nearly half of

45 Only 43 of the 85 subjects with germline mutations associated with a hereditary cancer s

46 Germline mutations associated with inherited diseases an

47 in we report analyses of 160 BRCA1 and BRCA2 germline mutation-associated breast and ovarian tumors.

48 However, not all BRCA1 and BRCA2 germline mutation-associated tumors respond.

49 In mice, introduction of a germline mutation at Bahcc1 to disrupt its H3K27me3 enga

50 Genetic screening for a germline mutation at the RET gene was performed in 11 fa

51 py regimen, patients without BRCA1 and BRCA2 germline mutations benefited from the addition of carbop

52 ents with MLH1 promoter hypermethylation and germline mutations, biallelic somatic inactivation was s

53 ndent tumors in two children with pathogenic germline mutations by genotyping somatic mutations share

54 led heterozygosity for the recurrent de novo germline mutation, c.148G > A, p.Asp50Asn.

55 arly identification of individuals who carry germline mutations can affect clinical care not only for

56 Recognition that germline mutations can predispose individuals to blood c

57 in normal breast tissues of BRCA1 and BRCA2 germline mutation carriers and in non-carrier controls,

58 t clinical utility of baseline WBMRI in TP53 germline mutation carriers and may form an integral part

59 ble estimates of cancer risk and spectrum in germline mutation carriers are essential for management.

60 prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016.

61 The incidence of germline mutation carriers in the general population or

62 turbations in normal breast tissues of BRCA1 germline mutation carriers may play a role in their high

63 adjusting for competing mortality, among all germline mutation carriers with the risk of progression

64 to all open chromatin regions in four DNMT3A germline mutation carriers, potentially due to TET2-medi

65 n cells from three additional unrelated TET2 germline mutation carriers.

66 = .02) and remained significant when BRCA1/2 germline mutations carriers were excluded (P = .021).

67 d individual-derived iPSCs showed that these germline mutations caused aberrant splicing of the endog

68 d expansion in primates-can introduce unique germline mutation clusters that can play a role in prima

69 e of thyroid cancer in CS patients with SDHx germline mutations compared to those with PTEN mutations

70 finger motifs in GATA-1, such as produced by germline mutations, compromises the function of this cri

71 rogenase genes (SDHx) co-occurring with PTEN germline mutations confer a 2-fold increased prevalence

72 not attributable to MLH1 hypermethylation or germline mutations contain 2 or more somatic mutations i

73 Purpose Deleterious germline mutations contribute to pancreatic cancer susce

74 Proportion of clinically actionable germline mutations detected by universal tumor-normal se

75 The frequency of germline mutations detected by using NGS has been report

76 cular processes that are altered by specific germline mutations, environmental exposures and related

77 families where probands lacked nonsynonymous germline mutations, especially in genes intolerant to mu

78 ence of dysplastic nevus syndrome and a BAP1 germline mutation extends the spectrum of the BAP1 tumor

79 rozygous N-ethyl-N-nitrosourea (ENU)-induced germline mutations for aberrant antigen-specific IgE and

80 tion [FM]) of deleterious autosomal dominant germline mutations for any syndrome.

81 The biology of neoplasia caused by germline mutations has led to paradigm-changing precisio

82 Study of the biology of tumors caused by germline mutations has led to recent paradigm-changing t

83 cted by colorectal adenomatous polyposis, no germline mutations have been identified in the previousl

84 nd ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from thera

85 ated in an ovarian cancer model with typical germline mutations (ID8 p53(-/-) brca2(-/-)), both in a

86 th breast cancer, 10.7% were found to have a germline mutation in a gene that predisposes women to br

87 oma viral oncogene homolog (KRAS)-variant, a germline mutation in a microRNA-binding site in KRAS, is

88 ic surveillance, 119 had a known deleterious germline mutation in a pancreatic cancer susceptibility

89 individuals with an identifiable deleterious germline mutation in a pancreatic cancer susceptibility

90 A germline mutation in CDH1 was identified in the index pa

91 Women who carry a germline mutation in either the BRCA1 or BRCA2 gene face

92 A double-hit mechanism, based on a primary germline mutation in one allele and a secondary somatic

93 loping colorectal tumors (CRTs) because of a germline mutation in one of their mismatch repair (MMR)

94 Here, we show that c.823C>T (p.Arg275Trp), a germline mutation in PARK2, is present in a family with

95 astoma cases are heritable, resulting from a germline mutation in RB1.

96 n, and his 13-year-old daughter, revealing a germline mutation in the BAP1 gene (c.592G>T, p.Glu198X)

97 ritable pulmonary arterial hypertension with germline mutation in the bone morphogenetic protein rece

98 In FD, a germline mutation in the Elp1 gene leads to Elp1 protein

99 Caused by a germline mutation in the NF1 tumor suppressor gene, indi

100 conclude that a homozygous loss-of-function germline mutation in the NTHL1 gene predisposes to a new

101 In total, 1 in 1000 individuals carries a germline mutation in the PKD1 or PKD2 gene, which leads

102 ed from a Gorlin syndrome patient carrying a germline mutation in the sonic hedgehog (SHH) receptor P

103 sk to an individual of carrying a pathogenic germline mutation in three mismatch repair (MMR) genes:

104 Finally, a loss-of-function germline mutation in UBE2T was detected in a high-risk b

105 Germline mutations in 14 genes have been associated with

106 roximately 40% of PPGLs are caused by driver germline mutations in 16 known susceptibility genes, and

107 blood samples were genotyped for somatic and germline mutations in APC and CTNNB1.

108 We investigated the prevalence of germline mutations in APC, ATM, BRCA1, BRCA2, CDKN2A, ML

109 Germline mutations in ATM (encoding the DNA-damage signa

110 To describe 8 new families with germline mutations in BAP1 and provide a comprehensive r

111 Individuals harboring inherited heterozygous germline mutations in BAP1 are predisposed to a range of

112 Patients with germline mutations in BAP1 may develop several flesh-col

113 Hereditary cases are associated with germline mutations in BMPR2 and 16 other genes; however,

114 Our results indicate that germline mutations in both coding and noncoding regions

115 Germline mutations in BRCA1 and BRCA2 are relatively com

116 types occurring in patients with deleterious germline mutations in BRCA1 or BRCA2 seem to be particul

117 DNA samples were analyzed for germline mutations in BRCA1, BRCA2, and 16 other cancer

118 Testing for germline mutations in BRCA1/2 is standard for select pat

119 Heterozygous germline mutations in BRCA2 predispose to breast and ova

120 Heterozygous germline mutations in breast cancer 1 (BRCA1) strongly p

121 s expression, the inheritance of monoallelic germline mutations in breast cancer susceptibility gene

122 amilies with a history of CRC, we associated germline mutations in BRF1 with predisposition to CRC.

123 Inactivating germline mutations in BTK cause a severe B-cell defect a

124 Germline mutations in cancer-predisposing genes were ide

125 Both carried homozygous germline mutations in CARD11 (p.Cys150*), impairing NF-k

126 Germline mutations in CDKN2A are frequently identified a

127 and ETV6) are the same as those that harbour germline mutations in children and adolescents who devel

128 The role of germline mutations in children and adults with hematolog

129 C19MC(2-4) was not amplified frequently had germline mutations in DICER1 or other microRNA-related a

130 Germline mutations in DNA damage repair (DDR) genes are

131 cluded owing to subsequent identification of germline mutations in DNA mismatch repair genes (n = 47)

132 Although the prevalence of germline mutations in DNA-repair genes among men with lo

133 Overall, the frequency of germline mutations in DNA-repair genes among men with me

134 The frequencies of germline mutations in DNA-repair genes among men with me

135 dhood overgrowth disorder that is defined by germline mutations in DNMT3A.

136 Tumors arising in patients who carry germline mutations in either BRCA1 or BRCA2 are sensitiv

137 Germline mutations in established moderately or highly p

138 f major interest following identification of germline mutations in Facio-Scapulo-Humeral Dystrophy (F

139 DNA from patients was analyzed for germline mutations in four telomere maintenance genes as

140 Germline mutations in fundamental epigenetic regulatory

141 plastic syndrome (MDS) and monosomy 7 harbor germline mutations in GATA2.

142 tients with OC, 347 (18%) carried pathogenic germline mutations in genes associated with OC risk.

143 ately 5% of all CRCs arise in the setting of germline mutations in genes involved in key cellular pro

144 In the last decade, discovery of germline mutations in genes involved in the PI3Kdelta pa

145 In our multicenter study, the incidence of germline mutations in genes mediating DNA-repair process

146 sonalize HR directed therapies in the clinic.Germline mutations in homologous recombination (HR) DNA

147 ides a centralized workflow for prioritizing germline mutations in human disease within a streamlined

148 We report germline mutations in human Piwi (Hiwi) in patients with

149 llows for the detection of BRCA and non-BRCA germline mutations in individuals with high risks of bre

150 The discovery of numerous somatic and germline mutations in ion channels in primary hyperaldos

151 The textbook view that most germline mutations in mammals arise from replication err

152 We identified germline mutations in MET, encoding a receptor tyrosine

153 patients had MBC with measurable disease and germline mutations in non-BRCA1/2 HR-related genes (coho

154 ng in the four remaining families identified germline mutations in noncoding sequences surrounding AC

155 iated with risk for colorectal cancer (CRC); germline mutations in NTHL1, RPS20, FANCM, FAN1, TP53, B

156 eature facilitated CRISPR-Cas9 generation of germline mutations in orco, the gene that encodes the ob

157 evidence of gene and disease association of germline mutations in PALB2 and MLH1 with hereditary pre

158 Conclusion Germline mutations in pancreatic cancer susceptibility g

159 Methods To define the prevalence of these germline mutations in patients with apparently sporadic

160 We identify NPM1 germline mutations in patients with dyskeratosis congeni

161 Patients with heterozygous germline mutations in phosphatase and tensin homolog del

162 age renal failure in humans and results from germline mutations in PKD1 or PKD2.

163 Germline mutations in poly(A)ribonuclease (PARN) cause a

164 Germline mutations in PTEN account for ~10% of cases of

165 e (CS), a disorder typically associated with germline mutations in PTEN.

166 Germline mutations in Ras pathway components are associa

167 Exome sequencing identified germline mutations in SDHA, which encodes succinate dehy

168 Rare germline mutations in SFXN4 lead to phenotypic character

169 Germline mutations in Shoc2 are associated with the huma

170 Human genetic studies have discovered germline mutations in single genes that instigate famili

171 (CTLN-II) is an inherited disorder caused by germline mutations in SLC25A13, manifesting clinically i

172 Germline mutations in SPRTN cause Ruijs-Aalfs syndrome (

173 e report cancer outcomes in individuals with germline mutations in telomerase and other telomere-main

174 Our findings identify germline mutations in telomerase as a Mendelian risk fac

175 Conversely, germline mutations in telomerase-relevant genes that dec

176 Similar to germline mutations in telomere biology genes leading to

177 ively referred to as TBD here) are caused by germline mutations in telomere biology genes leading to

178 ifetime cancer risks conferred by pathogenic germline mutations in that gene.

179 Germline mutations in the cadherin 1, type 1, E-cadherin

180 Germline mutations in the CARD11 gene result in at least

181 HDGC, which is mainly caused by germline mutations in the E-cadherin gene (CDH1), render

182 Germline mutations in the Folliculin (FLCN) tumour suppr

183 hydrogenase-1 or -2 (IDH1 or IDH2) genes, or germline mutations in the fumarate hydratase (FH) and su

184 We identified heterozygous germline mutations in the G protein-coupled receptor 161

185 The majority of SCN cases arise because of germline mutations in the gene elastase, neutrophil-expr

186 Individuals with germline mutations in the gene encoding phosphatase and

187 Germline mutations in the gene encoding tumor suppressor

188 Here, we report that germline mutations in the inflammasome sensor NLRP1 caus

189 Lynch syndrome, caused by germline mutations in the mismatch repair genes, is asso

190 compound-heterozygous loss-of-function (LoF) germline mutations in the mismatch-repair gene MSH3.

191 rm in the adult human heart is Na(V)1.5, and germline mutations in the Na(V)1.5-encoding gene, sodium

192 ble cancer predisposition syndrome caused by germline mutations in the NF1 tumor suppressor, which en

193 ent protocol for the generation of heritable germline mutations in the parasitoid jewel wasp, Nasonia

194 minant, hereditary cancer disorder caused by germline mutations in the RET (formerly MEN2A, MEN2B) pr

195 De novo germline mutations in the RNA helicase DDX3X account for

196 Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2

197 Germline mutations in the TGM1 gene, which encodes the e

198 Somatic or germline mutations in the tuberous sclerosis complex (TS

199 Brooke-Spiegler syndrome) carry germline mutations in the tumor suppressor CYLD and deve

200 common tumor-predisposition disorder due to germline mutations in the tumor suppressor gene NF1.

201 Germline mutations in the tumor suppressor Pten are a we

202 astoma is a rare pediatric cancer induced by germline mutations in the tumor suppressors RB1 or DICER

203 It is largely caused by inactivating germline mutations in the tumour suppressor gene CDH1, a

204 d in several skin-tumour syndromes caused by germline mutations in the tumour suppressor gene, CYLD.

205 identify the first FA patient with biallelic germline mutations in the ubiquitin E2 conjugase UBE2T.

206 adenomatous polyposis (FAP-iPSCs) harboring germline mutations in the WNT-signaling-pathway-regulato

207 Germline mutations in the X-linked gene, methyl-CpG-bind

208 Heterozygous germline mutations in the zinc finger transcription fact

209 ical management guidelines for patients with germline mutations in these 4 newly included genes are l

210 ar, generating several independent heritable germline mutations in this gene.

211 sease caused by high-penetrance heterozygous germline mutations in TNFAIP3, which encodes the NF-kapp

212 Germline mutations in TP53 cause a rare high penetrance

213 s a cancer predisposition disorder caused by germline mutations in TP53 that can lead to increased mi

214 ncer predisposition syndrome associated with germline mutations in TP53.

215 In humans, germline mutations in Trpm6 cause autosomal dominant hyp

216 osis and Noonan and Legius syndromes, harbor germline mutations in various RAS/mitogen-activated prot

217 frontotemporal dementia (IBMPFD) that harbor germline mutations in VCP, the levels of Shoc2 ubiquitin

218 al tumors who had 2 or more somatic (but not germline) mutations in genes encoding MMR proteins (doub

219 trial tumors with 2 or more somatic (but not germline) mutations in MMR proteins also have mutations

220 contain a larger-than-expected proportion of germline mutations, including previously unreported muta

221 rehensive genome-wide survey of the range of germline mutations induced in laboratory mice after pare

222 ersonalized reference genomes by integrating germline mutations into the reference genome.

223 For example, germline mutations involving BRCA1, BRCA2, PRSS1, and mi

224 A positive germline mutation is associated with an increased risk o

225 phenomenon where the pathogenic effect of a germline mutation is corrected by a second somatic event

226 ikingly, however, the degree of male bias in germline mutations is approximately 4:1, similar to that

227 checkpoint regulator, and the CHEK2*1100delC germline mutation leads to loss of function and increase

228 Pathogenic germline mutations occurred in eight PCC/PGL susceptibil

229 Germline mutation of BRCA2 induces hereditary pancreatic

230 Germline mutation of the BRCA1 associated protein-1 (BAP

231 We found that the predisposing germline mutation of the NF1 gene was frequently convert

232 All 4 patients had a germline mutation of the related gene PIGT and a somatic

233 In addition, two germline mutations of BRCA1 are found to disrupt the dim

234 Individuals with germline mutations of C/EBPepsilon fail to develop norma

235 (WES) has the potential to reveal tumor and germline mutations of clinical relevance, but the diagno

236 Germline mutations of DNA double-strand break (DSB) resp

237 ding of familial MDS/AML syndromes caused by germline mutations of hematopoietic transcription factor

238 ] age, 41.0 [13.3] years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TM

239 regions and genes disrupted by rare, de novo germline mutations of large effect.

240 Germline mutations of the BRCA1-associated protein-1 gen

241 l cell carcinoma (HLRCC) is characterized by germline mutations of the FH gene that encodes for the T

242 ullary thyroid cancer (MTC) can be caused by germline mutations of the RET proto-oncogene or occurs a

243 Germline mutations of the SMARCB1 gene predispose to two

244 harbors multiple conserved cis-elements, and germline mutations of these cis-elements are pathogenic

245 assess the impact of ATM/BRCA1/BRCA2/ PALB2 germline mutations on cause-specific survival (CSS) from

246 In this study, we assay the impact of rare germline mutations on CRC, analysing high-coverage exome

247 Germline mutation or deletion of the RB1 gene was identi

248 by CRISPR/Cas9 is commonly used to generate germline mutations or perform in vitro screens, but appl

249 uestions that remain for patients with these germline mutations or their treating clinicians include:

250 equencing identified two homozygous missense germline mutations, P733L and P832S, in the JAK1 protein

251 The mechanisms by which SMARCB1 germline mutations predispose to rhabdoid tumors versus

252 most two orders of magnitude higher than the germline mutation rate and that both mutation rates are

253 first time we determined the genome-wide STR germline mutation rate from a deeply sequenced human ped

254 The germline mutation rate has been extensively studied and

255 ncing (WGS) studies have estimated the human germline mutation rate per basepair per generation (~1.2

256 We estimate the simultaneous MNV germline mutation rate to be 1.78 x 10(-10) mutations pe

257 Here we estimate germline mutation rates and spectra in six multi-sibling

258 We conclude that germline mutation rates in healthy young adults may prov

259 Germline mutation rates in humans have been estimated fo

260 us to make the first direct comparison with germline mutation rates in these two species.

261 into question by revealing unexpectedly low germline mutation rates, which imply that substitutions

262 omatic mutations; frequencies of deleterious germline mutations related to patient phenotype and inci

263 e contributions of these mechanisms to human germline mutation remain unknown.

264 one unrelated individual with biallelic PMS2 germline mutations, representing constitutional mismatch

265 ts with breast cancer in the NYBCS carried a germline mutation responsible for their disease: 11.0% (

266 atic imaging was significantly higher in the germline mutation risk group (n = 134) than in the famil

267 ied, and whole-exome sequencing identified a germline mutation (S631G) at a highly conserved serine r

268 We introduce Germline Mutation Scoring Tool fOr Next-generation sEque

269 propose that transcriptional scanning shapes germline mutation signatures and modulates mutation rate

270 utations, we found remarkable consistency in germline mutation spectra between the sexes and at diffe

271 To determine whether BRCA1 and BRCA2 germline mutation status affects therapy response in pat

272 Whether BRCA1 and BRCA2 germline mutation status affects treatment outcome remai

273 uvant treatment according to BRCA1 and BRCA2 germline mutation status.

274 so featured GATA4 loss of function via GATA4 germline mutations that abrogated GATA4 interactions wit

275 t the different genetic pathways impacted by germline mutations that can ultimately lead to the devel

276 equirement in fibroblasts from patients with germline mutations that cause severely reduced levels of

277 of patient cases of CRC are associated with germline mutations that confer an inherited predispositi

278 h syndrome is caused by dominantly inherited germline mutations that predispose individuals to colore

279 nct from familial cysts due to a lack of the germline mutations that underlie familial cysts and a de

280 In inherited PD, PARK genes harbor germline mutations; the same genes are somatically mutat

281 nd cast further doubt on the assumption that germline mutations track cell divisions.

282 multiple renal tumors, each of whom had the germline mutation TSC2 p.R905Q.

283 A germline mutation was identified in 23 probands (53.5 +/

284 ifferentiation of somatic patient cells with germline mutations was a viable approach to generate LAM

285 None of the 5 most frequent germline mutations was identified in mosaic state.

286 The pathogenicity of all reported mosaic/germline mutations was reassessed according to internati

287 e and model the pathogenicity of these CDK10 germline mutations, we generated conditional-knockout mi

288 Deleterious germline mutations were also found in BUB1B (1) and BUB3

289 All of the germline mutations were associated with a severe phenoty

290 Moreover, many tumors harboring BAP1 germline mutations were associated with BAP1 syndrome, i

291 LS germline mutations were identified in 24.8% of patients

292 Pathogenic BRCA1 and BRCA2 germline mutations were present in 50 of the 291 patient

293 Germline mutations were present in 50% of children.

294 Patients with these germline mutations were younger than those without (mean

295 fect risk for the disease (ie, age and BRCA1 germline mutations), were significantly associated with

296 ssociated malignancies and were assessed for germline mutations when found to have MBAITs on dermatol

297 The remaining cases with germline mutations, which were predominantly missense mu

298 ing was performed using primers that flanked germline mutations, whose design did not rely on prior k

299 nd son) had co-occurrence of RUNX1 and CEBPA germline mutations, with variable AML disease onset at 5

300 to determine a potential association of LoF germline mutations within the FANCM gene with BC and/or