Polymorphism of Gly39Glu (c.116G&gt;A) hMSH6 is associated with sporadic
colorectal cancer development in the Polish population: Preliminary results

Zelga, Piotr; Przybyłowska-Sygut, Karolina; Zelga, Marta; Dziki, Adam; Majsterek, Ireneusz

doi:10.17219/acem/64877

Cited by 5 publications

(4 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The G39 has been associated with an increased risk of CRC according to the nucleic-acid data. [51] We identified G39 proteoforms of MSH6 in both SW480 and SW620 cells, but identified the E39 proteoform only in the SW480 cells, not in the SW620 cells.…”

Section: As Shown In Figuresmentioning

confidence: 69%

Qualitative and quantitative top-down proteomics of human colorectal cancer cell lines identified 23000 proteoforms and revealed drastic proteoform-level differences between metastatic and non-metastatic cancer cells

McCool

Chen

et al. 2021

Preprint

View full text Add to dashboard Cite

Understanding cancer metastasis at the proteoform level is crucial for discovering new protein biomarkers for cancer diagnosis and drug development. Proteins are the primary effectors of function in biology and proteoforms from the same gene can have drastically different biological functions. Here, we present the first qualitative and quantitative top-down proteomics (TDP) study of a pair of isogenic human metastatic and non-metastatic colorectal cancer (CRC) cell lines (SW480 and SW620). This study pursues a global view of human CRC proteome before and after metastasis in a proteoform specific manner. We identified 23,319 proteoforms of 2,297 genes from the CRC cell lines using capillary zone electrophoresis-tandem mass spectrometry (CZE-MS/MS), representing nearly one order of magnitude improvement in the number of proteoform identifications from human cell lines compared to literature data. We identified 111 proteoforms containing single amino acid variants (SAAVs) using a proteogenomic approach and revealed drastic differences between the metastatic and non-metastatic cell lines regarding SAAVs profiles. Quantitative TDP analysis unveiled statistically significant differences in proteoform abundance between the SW480 and SW620 cell lines on a proteome scale for the first time. Ingenuity Pathway Analysis (IPA) disclosed that many differentially expressed genes at the proteoform level had diversified functions and were closely related to cancer. Our study represents a milestone in TDP towards the definition of human proteome in a proteoform specific manner, which will transform basic and translational biomedical research.For TOC only

show abstract

Section: As Shown In Figuresmentioning

confidence: 69%

Qualitative and quantitative top-down proteomics of human colorectal cancer cell lines identified 23000 proteoforms and revealed drastic proteoform-level differences between metastatic and non-metastatic cancer cells

McCool

Chen

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…We identified one DNA mismatch repair protein Msh6 (MSH6) proteoform containing an SAAV due to polymorphism at position 39 (G → E). The G39E SAAV has been associated with an increased risk of CRC according to the nucleic acid data ( 48 ). We identified G39 proteoforms of MSH6 in both SW480 and SW620 cells but identified the E39 proteoform only in the SW480 cells not in the SW620 cells.…”

Section: Resultsmentioning

confidence: 99%

Deep top-down proteomics revealed significant proteoform-level differences between metastatic and nonmetastatic colorectal cancer cells

McCool

Chen

et al. 2022

Sci. Adv.

View full text Add to dashboard Cite

Understanding cancer metastasis at the proteoform level is crucial for discovering previously unknown protein biomarkers for cancer diagnosis and drug development. We present the first top-down proteomics (TDP) study of a pair of isogenic human nonmetastatic and metastatic colorectal cancer (CRC) cell lines (SW480 and SW620). We identified 23,622 proteoforms of 2332 proteins from the two cell lines, representing nearly fivefold improvement in the number of proteoform identifications (IDs) compared to previous TDP datasets of human cancer cells. We revealed substantial differences between the SW480 and SW620 cell lines regarding proteoform and single amino acid variant (SAAV) profiles. Quantitative TDP unveiled differentially expressed proteoforms between the two cell lines, and the corresponding genes had diversified functions and were closely related to cancer. Our study represents a pivotal advance in TDP toward the characterization of human proteome in a proteoform-specific manner, which will transform basic and translational biomedical research.

show abstract

“…While together with MSH3 rs26279 (Ala1045Thr) it has a protective role in BC patients, alone it acted as a risk factor for BC [ 73 , 123 ]. SNP rs1042821 was associated with decreased risk of primary hepatocellular cancer, and together with MSH3 rs26279 (Ala1045Thr) with decreased risk of oesophageal cancer; patients carrying the heterozygous G/A genotype of rs1042821 did not display higher risk of CRC (OR = 1.65, 95% CI = 1.01–2.69, p = 0.44) [ 124 , 125 ]. A recent case–control study comprising 106 thyroid cancer patients and 212 age- and gender-matched controls revealed that MSH6 rs1042821 variant homozygotes exhibited higher risk of this cancer (OR = 3.42, CI = 1.04–11.24, p = 0.04).…”

Section: Results On Mmr Gene Variantsmentioning

confidence: 99%

DNA Mismatch Repair Gene Variants in Sporadic Solid Cancers

Čaja

Vodičková

Král

et al. 2020

IJMS

View full text Add to dashboard Cite

The phenotypic effects of single nucleotide polymorphisms (SNPs) in the development of sporadic solid cancers are still scarce. The aim of this review was to summarise and analyse published data on the associations between SNPs in mismatch repair genes and various cancers. The mismatch repair system plays a unique role in the control of the genetic integrity and it is often inactivated (germline and somatic mutations and hypermethylation) in cancer patients. Here, we focused on germline variants in mismatch repair genes and found the outcomes rather controversial: some SNPs are sometimes ascribed as protective, while other studies reported their pathological effects. Regarding the complexity of cancer as one disease, we attempted to ascertain if particular polymorphisms exert the effect in the same direction in the development and treatment of different malignancies, although it is still not straightforward to conclude whether polymorphisms always play a clear positive role or a negative one. Most recent and robust genome-wide studies suggest that risk of cancer is modulated by variants in mismatch repair genes, for example in colorectal cancer. Our study shows that rs1800734 in MLH1 or rs2303428 in MSH2 may influence the development of different malignancies. The lack of functional studies on many DNA mismatch repair SNPs as well as their interactions are not explored yet. Notably, the concerted action of more variants in one individual may be protective or harmful. Further, complex interactions of DNA mismatch repair variations with both the environment and microenvironment in the cancer pathogenesis will deserve further attention.

show abstract

Polymorphism of Gly39Glu (c.116G>A) hMSH6 is associated with sporadic colorectal cancer development in the Polish population: Preliminary results

Cited by 5 publications

References 21 publications

Qualitative and quantitative top-down proteomics of human colorectal cancer cell lines identified 23000 proteoforms and revealed drastic proteoform-level differences between metastatic and non-metastatic cancer cells

Qualitative and quantitative top-down proteomics of human colorectal cancer cell lines identified 23000 proteoforms and revealed drastic proteoform-level differences between metastatic and non-metastatic cancer cells

Deep top-down proteomics revealed significant proteoform-level differences between metastatic and nonmetastatic colorectal cancer cells

DNA Mismatch Repair Gene Variants in Sporadic Solid Cancers

Contact Info

Product

Resources

About