MCID: LFR007
MIFTS: 47

Li-Fraumeni Syndrome 2

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Endocrine diseases, Cancer diseases

Aliases & Classifications for Li-Fraumeni Syndrome 2

MalaCards integrated aliases for Li-Fraumeni Syndrome 2:

Name: Li-Fraumeni Syndrome 2 57 75 29 6 73
Li-Fraumeni Syndrome 57 73
Lfs2 57 75
Li-Fraumeni Syndrome, Type 2 40

Characteristics:

HPO:

32
li-fraumeni syndrome 2:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Li-Fraumeni Syndrome 2

UniProtKB/Swiss-Prot : 75 Li-Fraumeni syndrome 2: A highly penetrant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.

MalaCards based summary : Li-Fraumeni Syndrome 2, also known as li-fraumeni syndrome, is related to li-fraumeni syndrome and adrenocortical carcinoma, hereditary. An important gene associated with Li-Fraumeni Syndrome 2 is CHEK2 (Checkpoint Kinase 2), and among its related pathways/superpathways are Chks in Checkpoint Regulation and Cell Cycle Checkpoints. The drugs Hyaluronic acid and Adjuvants, Immunologic have been mentioned in the context of this disorder. Affiliated tissues include brain, bone and testes, and related phenotypes are meningioma and breast carcinoma

Description from OMIM: 609265

Related Diseases for Li-Fraumeni Syndrome 2

Diseases in the Li-Fraumeni Syndrome family:

Li-Fraumeni Syndrome 2

Diseases related to Li-Fraumeni Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 73)
# Related Disease Score Top Affiliating Genes
1 li-fraumeni syndrome 33.9 CHEK2 TP53
2 adrenocortical carcinoma, hereditary 31.8 CHEK2 TP53
3 aging 29.8 CHEK2 TP53
4 hereditary breast ovarian cancer syndrome 29.4 CHEK2 TP53
5 ataxia-telangiectasia 29.2 CHEK2 TP53
6 myelodysplastic syndrome 28.8 CHEK2 TP53
7 gastric cancer 11.7
8 glioblastoma 11.5
9 soft tissue sarcoma 11.5
10 medulloblastoma 11.2
11 adrenal carcinoma 11.2
12 pilocytic astrocytoma 11.2
13 familial stomach cancer 11.2
14 sarcoma 10.4
15 breast cancer 10.4
16 choroiditis 10.4
17 adenocarcinoma 10.4
18 lung cancer susceptibility 3 10.3
19 melanoma 10.3
20 rhabdomyosarcoma 10.3
21 liposarcoma 10.2
22 choroid plexus cancer 10.2
23 ovarian cancer 10.1
24 lung cancer 10.1
25 leukemia 10.1
26 angiosarcoma 10.1
27 lymphoma 10.1
28 leiomyosarcoma 10.1
29 lynch syndrome 10.1
30 adrenal cortical adenocarcinoma 10.1
31 colorectal cancer 10.0
32 gastric cancer, hereditary diffuse 10.0
33 melanoma, cutaneous malignant 1 10.0
34 prostate cancer 10.0
35 autism 10.0
36 lymphoma, hodgkin, classic 10.0
37 immunodeficiency-centromeric instability-facial anomalies syndrome 1 10.0
38 myxoid liposarcoma 10.0
39 anaplastic large cell lymphoma 10.0
40 familial adenomatous polyposis 10.0
41 small cell carcinoma 10.0
42 mucosal melanoma 10.0
43 autism spectrum disorder 10.0
44 mucositis 10.0
45 prostatitis 10.0
46 peritoneal mesothelioma 10.0
47 breast sarcoma 10.0
48 astrocytoma 10.0
49 gliosarcoma 10.0
50 orbit rhabdomyosarcoma 10.0

Graphical network of the top 20 diseases related to Li-Fraumeni Syndrome 2:



Diseases related to Li-Fraumeni Syndrome 2

Symptoms & Phenotypes for Li-Fraumeni Syndrome 2

Clinical features from OMIM:

609265

Human phenotypes related to Li-Fraumeni Syndrome 2:

32
# Description HPO Frequency HPO Source Accession
1 meningioma 32 HP:0002858
2 breast carcinoma 32 HP:0003002
3 glioma 32 HP:0009733
4 stomach cancer 32 HP:0012126
5 sarcoma 32 HP:0100242

GenomeRNAi Phenotypes related to Li-Fraumeni Syndrome 2 according to GeneCards Suite gene sharing:

26 (show all 12)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-114 9.44 CHEK2
2 Increased shRNA abundance (Z-score > 2) GR00366-A-12 9.44 TP53
3 Increased shRNA abundance (Z-score > 2) GR00366-A-120 9.44 TP53 CHEK2
4 Increased shRNA abundance (Z-score > 2) GR00366-A-123 9.44 CHEK2
5 Increased shRNA abundance (Z-score > 2) GR00366-A-132 9.44 TP53
6 Increased shRNA abundance (Z-score > 2) GR00366-A-169 9.44 TP53
7 Increased shRNA abundance (Z-score > 2) GR00366-A-19 9.44 TP53
8 Increased shRNA abundance (Z-score > 2) GR00366-A-190 9.44 TP53
9 Increased shRNA abundance (Z-score > 2) GR00366-A-207 9.44 CHEK2
10 Increased shRNA abundance (Z-score > 2) GR00366-A-35 9.44 TP53
11 Increased shRNA abundance (Z-score > 2) GR00366-A-39 9.44 TP53
12 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.44 CHEK2

Drugs & Therapeutics for Li-Fraumeni Syndrome 2

Drugs for Li-Fraumeni Syndrome 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Hyaluronic acid Approved, Vet_approved Not Applicable 9004-61-9 53477741
2 Adjuvants, Immunologic Not Applicable
3 Protective Agents Not Applicable
4 Viscosupplements Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Safety and Effectiveness of Juvederm(R) Ultra XC Injectable Gel for Lip Augmentation Completed NCT01197495 Not Applicable

Search NIH Clinical Center for Li-Fraumeni Syndrome 2

Genetic Tests for Li-Fraumeni Syndrome 2

Genetic tests related to Li-Fraumeni Syndrome 2:

# Genetic test Affiliating Genes
1 Li-Fraumeni Syndrome 2 29 CHEK2

Anatomical Context for Li-Fraumeni Syndrome 2

MalaCards organs/tissues related to Li-Fraumeni Syndrome 2:

41
Brain, Bone, Testes, Lung, Breast, Skin, Cervix

Publications for Li-Fraumeni Syndrome 2

Articles related to Li-Fraumeni Syndrome 2:

(show top 50) (show all 290)
# Title Authors Year
1
Contribution of de novo and mosaic<i>TP53</i>mutations to Li-Fraumeni syndrome. ( 29070607 )
2018
2
Screening with whole-body magnetic resonance imaging in pediatric subjects with Li-Fraumeni syndrome: A single institution pilot study. ( 29077256 )
2018
3
The first two confirmed sub-Saharan African families with germline TP53 mutations causing Li-Fraumeni syndrome. ( 29392648 )
2018
4
Surveillance Screening in Li-Fraumeni Syndrome: Raising Awareness of False Positives. ( 29946497 )
2018
5
Misdiagnosis of Li-Fraumeni Syndrome in a Patient With Clonal Hematopoiesis and a Somatic <i>TP53</i> Mutation. ( 29752319 )
2018
6
Li-Fraumeni Syndrome-Related Malignancies Involving the Genitourinary Tract: Review of a Single-Institution Experience. ( 29935265 )
2018
7
What Should a Gynecologist Know about Li-Fraumeni Syndrome? Lessons from a Patient Undergoing Hysterectomy for Benign Indications. ( 29945152 )
2018
8
Association Between the Oligomeric Status of p53 and Clinical Outcomes in Li-Fraumeni Syndrome. ( 29955864 )
2018
9
Two cancer-predisposing variants in one family: Incidental finding of a fumarate hydrogenase (FH) germline variant in a family with Li-Fraumeni syndrome. ( 29893455 )
2018
10
A novel dysfunctional germline P53 mutation identified in a family with Li-Fraumeni syndrome. ( 29416929 )
2018
11
Revisiting tumor patterns and penetrance in germline TP53 mutation carriers: temporal phases of Li-Fraumeni syndrome. ( 29076966 )
2018
12
Radiation-associated Angiosarcoma Mimicking Fallopian Tube High-grade Serous Carcinoma in a Woman With De Novo Li-Fraumeni Syndrome. ( 29620582 )
2018
13
Successful Treatment of Recurrent Li-Fraumeni Syndrome-related Choroid Plexus Carcinoma. ( 28859040 )
2017
14
Colon Pathology Characteristics in Li-Fraumeni Syndrome. ( 28624650 )
2017
15
A novel TP53 germline inframe deletion identified in a Spanish series of Li-fraumeni syndrome suspected families. ( 28573494 )
2017
16
Autism spectrum disorder and Li-Fraumeni syndrome: purely coincidental or mechanistically associated? ( 28983852 )
2017
17
Pleomorphic myxoid liposarcoma in an adolescent with Li-Fraumeni syndrome. ( 28160093 )
2017
18
Inhibiting mitochondrial respiration prevents cancer in a mouse model of Li-Fraumeni syndrome. ( 27869650 )
2017
19
Association of Li-Fraumeni Syndrome With Small Cell Carcinoma of the Ovary, Hypercalcemic Type and Concurrent Pleomorphic Liposarcoma of the Cervix. ( 28177947 )
2017
20
Familial Melanoma Associated with Li-Fraumeni Syndrome and Atypical Mole Syndrome: Total-body Digital Photography, Dermoscopy and Confocal Microscopy. ( 28218344 )
2017
21
Prevalence of Cancer at Baseline Screening in the National Cancer Institute Li-Fraumeni Syndrome Cohort. ( 28772286 )
2017
22
Inherited TP53 Mutations and the Li-Fraumeni Syndrome. ( 28270529 )
2017
23
Breast cancer in patients with Li-Fraumeni syndrome - a case-series study and review of literature. ( 28356770 )
2017
24
Li-Fraumeni Syndrome Disease Model: A Platform to Develop Precision Cancer Therapy Targeting Oncogenic p53. ( 28818333 )
2017
25
Allele-specific wild-type TP53 expression in the unaffected carrier parent of children with Li-Fraumeni syndrome. ( 28279309 )
2017
26
Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome. ( 28572266 )
2017
27
Cancer Screening in Li-Fraumeni Syndrome. ( 28772307 )
2017
28
The psychosocial effects of the Li-Fraumeni Education and Early Detection (LEAD) program on individuals with Li-Fraumeni syndrome. ( 28301458 )
2017
29
Frequency of Thyroid Carcinoma in Brazilian TP53 p.R337H Carriers With Li Fraumeni Syndrome. ( 28114597 )
2017
30
Surveillance of Dutch Patients With Li-Fraumeni Syndrome: The LiFe-Guard Study. ( 28772294 )
2017
31
Nodular Lymphocyte-predominant Hodgkin Lymphoma in a 15-Year-Old Boy With Li-Fraumeni Syndrome Having a Germline TP53 D49H Mutation. ( 28902083 )
2017
32
Li-Fraumeni syndrome presenting as mucosal melanoma: Case report and treatment considerations. ( 27726232 )
2017
33
Estimating TP53 Mutation Carrier Probability in Families with Li-Fraumeni Syndrome Using LFSPRO. ( 28137790 )
2017
34
Li-Fraumeni versus Pseudo-Li-Fraumeni Syndrome: Key Insights for Interpreting Next-Generation Sequencing Reports in Patients with Suspected Cancer Predisposition Syndromes. ( 28592622 )
2017
35
Baseline Surveillance in Li-Fraumeni Syndrome Using Whole-Body Magnetic Resonance Imaging: A Meta-analysis. ( 28772291 )
2017
36
Primary Cutaneous Leiomyosarcoma Arising in a Patient With Li-Fraumeni Syndrome. A Neoplasm With Unusual Histopathologic Features and Loss of Heterozygosity at TP53 Gene. ( 28475508 )
2017
37
Whole body magnetic resonance imaging (WB-MRI) and brain MRI baseline surveillance in TP53 germline mutation carriers: experience from the Li-Fraumeni Syndrome Education and Early Detection (LEAD) clinic. ( 28988289 )
2017
38
Lung Adenocarcinoma as Part of the Li-Fraumeni Syndrome Spectrum: Preliminary Data of the LIFSCREEN Randomized Clinical Trial. ( 28772306 )
2017
39
Is Li-Fraumeni syndrome really much more common? ( 29091331 )
2017
40
Increasing genomic instability during cancer therapy in a patient with Li-Fraumeni syndrome. ( 29594232 )
2017
41
Should Genetic Testing be Offered for Children? The Perspectives of Adolescents and Emerging Adults in Families with Li-Fraumeni Syndrome. ( 28303452 )
2017
42
The Features of Colorectal Tumors in a Patient with Li-Fraumeni Syndrome. ( 28154273 )
2017
43
Atypical cutaneous melanocytic tumours arising in two patients with Li-Fraumeni syndrome. ( 29108654 )
2017
44
Hsp90 and PKM2 Drive the Expression of Aromatase in Li-Fraumeni Syndrome Breast Adipose Stromal Cells. ( 27467582 )
2016
45
Genetic and functional analysis of a Li Fraumeni syndrome family in China. ( 26818906 )
2016
46
Super-Transactivation TP53 Variant in the Germline of a Family with Li-Fraumeni Syndrome. ( 27297285 )
2016
47
Multiple primary tumors in a family with Li-Fraumeni syndrome with a TP53 germline mutation identified by next-generation sequencing. ( 27516001 )
2016
48
Does PTEN gene mutation play any role in Li-Fraumeni syndrome. ( 27493922 )
2016
49
Rare germline variant (rs78378222) in the TP53 3' UTR: Evidence for a new mechanism of cancer predisposition in Li-Fraumeni syndrome. ( 26823150 )
2016
50
Biochemical and imaging surveillance in Li-Fraumeni syndrome - Authors' reply. ( 27819240 )
2016

Variations for Li-Fraumeni Syndrome 2

UniProtKB/Swiss-Prot genetic disease variations for Li-Fraumeni Syndrome 2:

75
# Symbol AA change Variation ID SNP ID
1 CHEK2 p.Arg145Trp VAR_008554 rs137853007

ClinVar genetic disease variations for Li-Fraumeni Syndrome 2:

6
(show all 16)
# Gene Variation Type Significance SNP ID Assembly Location
1 CHEK2 CHEK2, 1-BP DEL, 1100C deletion Pathogenic,risk factor
2 CHEK2 NM_007194.3(CHEK2): c.470T> C (p.Ile157Thr) single nucleotide variant risk factor rs17879961 GRCh37 Chromosome 22, 29121087: 29121087
3 CHEK2 NM_007194.3(CHEK2): c.470T> C (p.Ile157Thr) single nucleotide variant risk factor rs17879961 GRCh38 Chromosome 22, 28725099: 28725099
4 CHEK2 NM_007194.3(CHEK2): c.433C> T (p.Arg145Trp) single nucleotide variant Likely pathogenic rs137853007 GRCh37 Chromosome 22, 29121242: 29121242
5 CHEK2 NM_007194.3(CHEK2): c.433C> T (p.Arg145Trp) single nucleotide variant Likely pathogenic rs137853007 GRCh38 Chromosome 22, 28725254: 28725254
6 CHEK2 CHEK2, 1-BP DEL, 1422T deletion Pathogenic
7 CHEK2 NM_007194.3(CHEK2): c.1283C> T (p.Ser428Phe) single nucleotide variant risk factor rs137853011 GRCh37 Chromosome 22, 29091207: 29091207
8 CHEK2 NM_007194.3(CHEK2): c.1283C> T (p.Ser428Phe) single nucleotide variant risk factor rs137853011 GRCh38 Chromosome 22, 28695219: 28695219
9 TP53 NM_000546.5(TP53): c.743G> A (p.Arg248Gln) single nucleotide variant Pathogenic/Likely pathogenic rs11540652 GRCh37 Chromosome 17, 7577538: 7577538
10 TP53 NM_000546.5(TP53): c.743G> A (p.Arg248Gln) single nucleotide variant Pathogenic/Likely pathogenic rs11540652 GRCh38 Chromosome 17, 7674220: 7674220
11 TP53 NM_000546.5(TP53): c.659A> G (p.Tyr220Cys) single nucleotide variant Pathogenic rs121912666 GRCh37 Chromosome 17, 7578190: 7578190
12 TP53 NM_000546.5(TP53): c.659A> G (p.Tyr220Cys) single nucleotide variant Pathogenic rs121912666 GRCh38 Chromosome 17, 7674872: 7674872
13 CHEK2 NM_007194.3(CHEK2): c.319+2T> A single nucleotide variant Likely pathogenic rs587782401 GRCh37 Chromosome 22, 29130389: 29130389
14 CHEK2 NM_007194.3(CHEK2): c.319+2T> A single nucleotide variant Likely pathogenic rs587782401 GRCh38 Chromosome 22, 28734401: 28734401
15 CHEK2 NM_007194.3(CHEK2): c.170C> T (p.Ser57Phe) single nucleotide variant Uncertain significance rs730881695 GRCh38 Chromosome 22, 28734552: 28734552
16 CHEK2 NM_007194.3(CHEK2): c.170C> T (p.Ser57Phe) single nucleotide variant Uncertain significance rs730881695 GRCh37 Chromosome 22, 29130540: 29130540

Cosmic variations for Li-Fraumeni Syndrome 2:

9
# Cosmic Mut ID Gene Symbol COSMIC Disease Classification
(Primary site, Site subtype, Primary histology, Histology subtype)
Mutation CDS Mutation AA GRCh38 Location Conf
1 COSM6954017 NOTCH2 soft tissue,breast,sarcoma,NS c.1145A>G p.N382S 1:119968196-119968196 3
2 COSM1732355 H3F3A soft tissue,bone,sarcoma,NS c.103G>T p.G35W 1:226064454-226064454 3
3 COSM3908208 GNAQ soft tissue,bone,sarcoma,NS c.442C>T p.R148* 9:77815650-77815650 3
4 COSM3908209 soft tissue,bone,sarcoma,NS c.355C>T p.R119* 9:77815650-77815650 3
5 COSM10646 TP53 central nervous system,choroid plexus,other,choroid plexus carcinoma c.725G>A p.C242Y 17:7674238-7674238 2
6 COSM10889 TP53 central nervous system,choroid plexus,other,choroid plexus carcinoma c.536A>G p.H179R 17:7675076-7675076 2
7 COSM10662 TP53 central nervous system,choroid plexus,other,choroid plexus carcinoma c.743G>A p.R248Q 17:7674220-7674220 2
8 COSM1104 SMARCB1 central nervous system,choroid plexus,other,choroid plexus carcinoma c.233-1G>C p.? 22:23793558-23793558 2

Expression for Li-Fraumeni Syndrome 2

Search GEO for disease gene expression data for Li-Fraumeni Syndrome 2.

Pathways for Li-Fraumeni Syndrome 2

Pathways related to Li-Fraumeni Syndrome 2 according to GeneCards Suite gene sharing:

(show all 21)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.21 CHEK2 TP53
2
Show member pathways
12.16 CHEK2 TP53
3 12.06 CHEK2 TP53
4
Show member pathways
12 CHEK2 TP53
5 11.97 CHEK2 TP53
6
Show member pathways
11.93 CHEK2 TP53
7 11.91 CHEK2 TP53
8
Show member pathways
11.9 CHEK2 TP53
9
Show member pathways
11.8 CHEK2 TP53
10 11.71 CHEK2 TP53
11 11.68 CHEK2 TP53
12
Show member pathways
11.42 CHEK2 TP53
13
Show member pathways
11.38 CHEK2 TP53
14
Show member pathways
11.3 CHEK2 TP53
15 11.22 CHEK2 TP53
16 11.14 CHEK2 TP53
17
Show member pathways
11.05 CHEK2 TP53
18 10.92 CHEK2 TP53
19
Show member pathways
10.81 CHEK2 TP53
20 10.6 CHEK2 TP53
21 9.32 CHEK2 TP53

GO Terms for Li-Fraumeni Syndrome 2

Cellular components related to Li-Fraumeni Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 PML body GO:0016605 8.62 CHEK2 TP53

Biological processes related to Li-Fraumeni Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular response to DNA damage stimulus GO:0006974 9.48 CHEK2 TP53
2 regulation of apoptotic process GO:0042981 9.46 CHEK2 TP53
3 regulation of signal transduction by p53 class mediator GO:1901796 9.43 CHEK2 TP53
4 cellular response to drug GO:0035690 9.4 CHEK2 TP53
5 DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest GO:0006977 9.37 CHEK2 TP53
6 response to gamma radiation GO:0010332 9.32 CHEK2 TP53
7 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator GO:0042771 9.26 CHEK2 TP53
8 cellular response to gamma radiation GO:0071480 9.16 CHEK2 TP53
9 DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator GO:0006978 8.96 CHEK2 TP53
10 replicative senescence GO:0090399 8.62 CHEK2 TP53

Molecular functions related to Li-Fraumeni Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein kinase binding GO:0019901 8.96 CHEK2 TP53
2 ubiquitin protein ligase binding GO:0031625 8.62 CHEK2 TP53

Sources for Li-Fraumeni Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....