Identification of <i>SPRY4</i> as a Novel Candidate Susceptibility Gene for Familial Nonmedullary Thyroid Cancer

Marques, Inês J.; Gomes, I; Pojo, Marta; Pires, Carolina; Moura, Margarida Maria; Cabrera, Rafael; Santos, Catarina; IJcken, Wilfred F. J. van; Teixeira, Manuel R.; Ramalho, José C.; Leite, Valeriano; Cavaco, Branca

doi:10.1089/thy.2020.0290

Cited by 11 publications

(13 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As first step, we mined the literature for candidate non-syndromic FNMTC susceptibility genes. In total, we identified 114 candidate genes across 32 independent studies ( 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 30 , 31 , 33 , 34 , 35 , 36 , 37 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ). A list of included genes and studies is provided in Supplementary data (Supplementary Table 1, see section on supplementary materials given at the end of this article).…”

Section: Resultsmentioning

confidence: 99%

“…The analysis of different kindreds with FNMTC advocates for an autosomal dominant inheritance with incomplete penetrance and variable expressivity ( 1 , 4 , 5 , 6 , 7 , 8 ). In the past years, several studies reported FNMTC-associated chromosomal loci ( 3 , 15 , 16 , 17 , 18 ) and predisposing risk variants in over 100 genes, including SRGAP1 , CHEK2 , SRRM2 , TIFF-1/NKX2 , FOXE1 , NOP53 , HABP2 , ANO7 , CAV2 , KANK1 , PIK3CB , PKD1L1 , PTPRF , BROX , RHBDD2 , ATM , MAP2K5 , EWSR1 , POT1 , TIAM1 and SPRY4 ( 1 , 3 , 7 , 12 , 15 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ). Recently, using whole-genomic sequencing, a group has identified variants in genes that were enriched in tumourigenic signalling pathways such as MAPK/ERK and PI3K/AKT in families with NMTC ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of NID1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing

Mello

Carneiro

Araújo

et al. 2022

Endocrine Connections

View full text Add to dashboard Cite

The genetics underlying non-syndromic familial non-medullary thyroid carcinoma (FNMTC) is still poorly understood. To identify susceptibility genes for FNMTC, we performed whole exome sequencing (WES) in a Brazilian family affected by papillary thyroid carcinoma (PTC) in three consecutive generations. WES was performed in four affected and two unaffected family members. Manual inspection in over 100 previously reported susceptibility genes for FNMTC showed that no variants in known genes co-segregated with disease phenotype in this family. Novel candidate genes were investigated using PhenoDB and filtered using Genome Aggregation (gnomAD) and Online Archive of Brazilian Mutations (ABraOM) population databases. The missense variant p.Ile657Met in the NID1 gene was the only variant that co-segregated with the disease, while absent in unaffected family members and controls. The allele frequency for this variant was <0.0001 in the gnomAD and ABbraOM databases. In silico analysis predicted the variant to be deleterious or likely damaging to the protein function. Somatic mutations in NID1 gene were found in nearly 500 cases of different cancer subtypes in the intOGen platform. Immunohistochemistry analysis showed NID1 expression in PTC cells, while it was absent in normal thyroid tissue. Our findings were corroborated using data from the TCGA cohort. Moreover, higher expression of NID1 was associated with higher likelihood of relapse after treatment and N1b disease in PTCs from the TCGA cohort. Although replication studies are needed to better understand the role of this variant in the FNMTC susceptibility, the NID1 variant (c.1971T>G) identified in this study fulfills several criteria that suggest it as a new FNMTC predisposing gene.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of NID1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing

Mello

Carneiro

Araújo

et al. 2022

Endocrine Connections

View full text Add to dashboard Cite

show abstract

“…Another SPRY4 protein variant is generated when the cytosine at the 701st nucleotide position in the SPRY4 coding sequence mutates to thymine, resulting in threonine-to-methionine substitution at amino acid residue 234. This variant promotes the proliferation of thyroid cancer cells ( 58 ). ②mRNA and protein stability: In non-small cell lung cancer, significantly upregulated KSRP protein promotes rapid decay of SPRY4 mRNA, leading to increased cell proliferation, migration, and invasion, thereby promoting lung cancer development ( 59 ).…”

Section: The Role Of Spry4 In Malignant Tumorsmentioning

confidence: 99%

Role of SPRY4 in health and disease

Pan,

Xu,

Zhang

2024

Front. Oncol.

View full text Add to dashboard Cite

SPRY4 is a protein encoding gene that belongs to the Spry family. It inhibits the mitogen-activated protein kinase (MAPK) signaling pathway and plays a role in various biological functions under normal and pathological conditions. The SPRY4 protein has a specific structure and interacts with other molecules to regulate cellular behavior. It serves as a negative feedback inhibitor of the receptor protein tyrosine kinases (RTK) signaling pathway and interferes with cell proliferation and migration. SPRY4 also influences inflammation, oxidative stress, and cell apoptosis. In different types of tumors, SPRY4 can act as a tumor suppressor or an oncogene. Its dysregulation is associated with the development and progression of various cancers, including colorectal cancer, glioblastoma, hepatocellular carcinoma, perihilar cholangiocarcinoma, gastric cancer, breast cancer, and lung cancer. SPRY4 is also involved in organ development and is associated with ischemic diseases. Further research is ongoing to understand the expression and function of SPRY4 in specific tumor microenvironments and its potential as a therapeutic target.

show abstract

“…Marques et al. ( 79 ) performed WES on leukocyte DNA from six affected members of FNMTC family. Shared genetic variants were identified through bioinformatic analysis and validated using Sanger sequencing.…”

Section: Identified Susceptibility Genes Associated With Fnmtcmentioning

confidence: 99%

Chromosomal localization of mutated genes in non-syndromic familial thyroid cancer

Jiang,

Xia,

Han

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

Familial non-medullary thyroid carcinoma (FNMTC) is a type of thyroid cancer characterized by genetic susceptibility, representing approximately 5% of all non-medullary thyroid carcinomas. While some cases of FNMTC are associated with familial multi-organ tumor predisposition syndromes, the majority occur independently. The genetic mechanisms underlying non-syndromic FNMTC remain unclear. Initial studies utilized SNP linkage analysis to identify susceptibility loci, including the 1q21 locus, 2q21 locus, and 4q32 locus, among others. Subsequent research employed more advanced techniques such as Genome-wide Association Study and Whole Exome Sequencing, leading to the discovery of genes such as IMMP2L, GALNTL4, WDR11-AS1, DUOX2, NOP53, MAP2K5, and others. But FNMTC exhibits strong genetic heterogeneity, with each family having its own pathogenic genes. This is the first article to provide a chromosomal landscape map of susceptibility genes associated with non-syndromic FNMTC and analyze their potential associations. It also presents a detailed summary of variant loci, characteristics, research methodologies, and validation results from different countries.

show abstract

Identification of SPRY4 as a Novel Candidate Susceptibility Gene for Familial Nonmedullary Thyroid Cancer

Cited by 11 publications

References 47 publications

Identification of NID1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing

Identification of NID1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing

Role of SPRY4 in health and disease

Chromosomal localization of mutated genes in non-syndromic familial thyroid cancer

Contact Info

Product

Resources

About