Mismatch DNA repair mRNA expression profiles in oral melanin pigmentation lesion and hamartomatous polyp of a child with peutz–jeghers syndrome

Vageli, Dimitra P.; Doukas, Sotirios G.; Markou, Andreas

doi:10.1002/pbc.24579

Cited by 4 publications

(3 citation statements)

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“…It is clear that balanced expression levels of components of the MMR system are essential for effective repair functions (2,32,45). Vageli et al previously demonstrated an association between an imbalanced mRNA phenotype of MMR genes and cancer progression in human lung, colorectal and urinary bladder cancer (18,(46)(47)(48)(49).…”

mentioning

confidence: 99%

Role of DNA mismatch repair genes in lung and head and neck cancer (Review)

Doukas

Vageli²,

Νikolouzakis

et al. 2019

Wrld Acd Sci

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The role of the DNA repair mechanism is to protect genetic material from destabilization. A defect in the DNA mismatch repair (MMR) mechanism has been associated with both hereditary and sporadic tumors. The dysregulation of MMR gene expression has been reported in lung, and in head and neck sporadic tumors. However, the mechanisms through which defects in the DNA MMR mechanism promote lung, and head and neck cancer remain unclear. Environmental factors and epigenetic alterations can significantly alter the ability of cells to repair genetic damage. The loss or a low expression of MMR genes allows for the survival of cells carrying a significant amount of genetic alterations, some in proto-oncogenes or genes regulating the cell cycle. The dysregulation or malfunction of the MMR mechanism has also been linked to alterations in response to chemotherapy. The investigation of MMR dysregulations in lung, and head and neck carcinomas may contribute to a better understanding of their biological role in the development and progression of these types of cancer, and may thus also improve their diagnostic, prognostic and therapeutic value.

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mentioning

confidence: 99%

Role of DNA mismatch repair genes in lung and head and neck cancer (Review)

Doukas

Vageli²,

Νikolouzakis

et al. 2019

Wrld Acd Sci

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“…Studies have shown that repairing specific types of DNA damage requires SLX4 and other endonucleases to participate together[ 22 ]. At present, it is believed that[ 27 - 29 ] the loss of DNA MMR genes causes the accumulation of mismatches in the process of DNA replication, resulting in the occurrence of microsatellite instability and partial junctions. Colorectal cancer has obvious genetic characteristics.…”

Section: Discussionmentioning

confidence: 99%

Detection and analysis of common pathogenic germline mutations in Peutz-Jeghers syndrome

Zhang

et al. 2021

WJG

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BACKGROUND Different types of pathogenic mutations may produce different clinical phenotypes, but a correlation between Peutz-Jeghers syndrome (PJS) genotype and clinical phenotype has not been found. Not all patients with PJS have detectable mutations of the STK11/LKB1 gene, what is the genetic basis of clinical phenotypic heterogeneity of PJS? Do PJS cases without STK11/LKB1 mutations have other pathogenic genes? Those are clinical problems that perplex doctors. AIM The aim was to investigate the specific gene mutation of PJS, and the correlation between the genotype and clinical phenotype of PJS. METHODS A total of 24 patients with PJS admitted to the Air Force Medical Center, PLA (formerly the Air Force General Hospital, PLA) from November 1994 to January 2020 were randomly selected for inclusion in the study. One hundred thirty-nine common hereditary tumor-related genes including STK11/LKB1 were screened and analyzed for pathogenic germline mutations by high-throughput next-generation sequencing (NGS). The mutation status of the genes and their relationship with clinical phenotypes of PJS were explored. RESULTS Twenty of the 24 PJS patients in this group (83.3%) had STK11/LKB1 gene mutations, 90% of which were pathogenic mutations, and ten had new mutation sites. Pathogenic mutations in exon 7 of STK11/LKB1 gene were significantly lower than in other exons. Truncation mutations are more common in exons 1 and 4 of STK11/LKB1 , and their pathogenicity was significantly higher than that of missense mutations. We also found SLX4 gene mutations in PJS patients. CONCLUSION PJS has a relatively complicated genetic background. Changes in the sites responsible for coding functional proteins in exon 1 and exon 4 of STK11/LKB1 may be one of the main causes of PJS. Mutation of the SLX4 gene may be a cause of genetic heterogeneity in PJS.

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“…Pigmentation features may mimic xeroderma pigmentosum in the early stages (xeroderma pigmentosum is an extreme sun sensitivity-associated high risk of skin cancer) (19). Melanin hyperpigmentation present on a patient who is not previously known to have the syndrome must be biopsied in order to obtain a clear diagnostic (20). Previous findings have revealed a certain genotype-phenotype correlation of the STK11/LKB1 gene involving the fact that more severe dermatological findings are correlated with a more aggressive profile of gastro-intestinal hamartomatous polyps (21).…”

Section: Skin and Mucosal Manifestationsmentioning

confidence: 99%

Peutz‑Jeghers syndrome: Skin manifestations and endocrine anomalies (Review)

et al. 2021

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Peutz-Jeghers syndrome (PJS), a rare autosomal dominant serine/threonine kinase 11 (STK11)/ liver kinase B1 (LKB1) gene-related genodermatosis, is characterized by oral hyperpigmentation (OHP); multiple gastro-intestinal mucosal benign hamartomatous polyps causing local bleeding, occlusion, intussusception, post-resection small bowel syndrome, associated increased risk of small intestinal cancer (incidence during the third decade); and 76% cumulative higher risk than the global population of developing non-gastrointestinal tumors (female predominance) including ovarian/testicular neoplasia, pancreatic and gynecologic (breast, uterus, ovarian) cancers. Suggestive PJS-associated OHP requires STK11 genetic testing. Abdominal pain in an OHP patient may be related to PJS-associated polyps. Other features include focal depigmentation followed by hyperpigmentation, and xeroderma pigmentosum-like lesions. The severity of the dermatological findings is correlated with gastrointestinal polyps. The STK11 gene is linked to reserve of primordial follicles, polycystic ovary syndrome, female fertility, and spermatogenesis. PJS is associated with 2 types of ovarian sex-cord stroma tumors (SCSTs): annular tubules (SCTATs) and pure Sertoli cell tumors. SCSTs accounts for 8% of ovarian cancer and SCTATs represents 2% of SCST, which may be associated with the overproduction of progesterone. PJS-SCTAT vs. non-PJS-SCTAT reveals bilateral/multifocal, small tumors with a benign behavior vs. a unique ovarian, large tumor with increased malignant/metastasis risk. Male precocious puberty is due to large cell calcifying Sertoli cell tumors (LCCSCTs). Notably, 30-40% of LCCSCTs are caused by PJS or Carney complex. PJS-LCCSCT is not aggressive, but it may be bilateral/multifocal, with the ultrasound hallmark being micro-calcifications. Testicular, intra-tubular large cell hyalinizing Sertoli cell tumor is the second testicle neoplasia in PJS. The skin and mucosal lesions are useful markers of PJS, assisting with the early identification of hamartomatouspolyps and initiation of serial surveillance of ovarian, or testicular neoplasia.

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Mismatch DNA repair mRNA expression profiles in oral melanin pigmentation lesion and hamartomatous polyp of a child with peutz–jeghers syndrome

Cited by 4 publications

References 9 publications

Role of DNA mismatch repair genes in lung and head and neck cancer (Review)

Role of DNA mismatch repair genes in lung and head and neck cancer (Review)

Detection and analysis of common pathogenic germline mutations in Peutz-Jeghers syndrome

Peutz‑Jeghers syndrome: Skin manifestations and endocrine anomalies (Review)

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