Novel germline STK11 variants and breast cancer phenotype identified in an Indian cohort of Peutz–Jeghers syndrome

Lipsa, Anuja; Kowtal, Pradnya; Sarin, Rajiv

doi:10.1093/hmg/ddz027

Cited by 17 publications

(11 citation statements)

References 38 publications

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“…Previous publications have proved the relationship between LKB1 germline mutation and PJS [1,[7][8][9]14]. In most of the PJS patients, LKB1 exon mutation could be detected either through PCR based Sanger sequencing [6] or multiplex ligation-dependent probe amplification (MLPA) [15], or even whole exome sequencing [16]. The published mutation rate varies from 66 to 94% [17].…”

Section: Discussionmentioning

confidence: 99%

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Distinct promoter methylation patterns of LKB1 in the hamartomatous polyps of Peutz-Jeghers syndrome and its potential in gastrointestinal malignancy prediction

Lin

Zhao

et al. 2020

Orphanet J Rare Dis

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Background: Peutz-Jeghers Syndrome (PJS) is known as a rare inherited polyposis due to the malfunction of serine/threonine kinase gene LKB1. However, not all of PJS patients carry LKB1 germline mutation. Previous researches have observed the elevated DNA methylation level in PJS polyps. Nevertheless, the mechanism of such abnormal and its impact on PJS patients remains to be fully described. Results: The results proved a significant increase on the methylation level of LKB1 promoter in PJS polyps compared with normal colon biopsies through bisulfite PCR followed by Sanger sequencing. Moreover, the methylation pattern in PJS polyps could be further categorized as three different scenarios: hypermethylated, hemimethylated and hypomethylated pattern. Furthermore, immunohistochemistry of DNMT1/3a/3b suggested the up-regulation of DNMT1 and 3a might participate the epigenetic alternation of LKB1 in PJS polyps. Logistic regression suggested hypomethylated LKB1 promoter in PJS polyps as a risk factor for gastrointestinal malignancies in PJS patients. Conclusions: The promoter methylation level of LKB1 gene in PJS polyps is generally elevated compared with normal colon mucosa. Yet not all of PJS polyps carry hypermethylated LKB1 promoter. Hypomethylation in this region has linked to malignant tumors in PJS patients. Given the rarity of PJS, this work together with previous researches, have proved the importance of LKB1 promoter methylation in PJS development and prognosis.

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Section: Discussionmentioning

confidence: 99%

“…Although previous researches have proved the majority of PJS patients carry LKB1 exon mutation [6][7][8][9], others suggested LKB1 mutation might not be the only explanation [10]. In 2000, researchers use methylation specific PCR (MSP) method first detected aberrant DNA methylation in PJS patients [11].…”

Section: Introductionmentioning

confidence: 99%

Distinct promoter methylation patterns of LKB1 in the hamartomatous polyps of Peutz-Jeghers syndrome and its potential in gastrointestinal malignancy prediction

Lin

Zhao

et al. 2020

Orphanet J Rare Dis

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“…In 2018, Chiang et al and Fostira et al reported respectively BC in 2/8 and 3/10 female PJS patients [38,76]. Lipsa et al reported BC in 4/7 women with a PV in STK11 and in 5/8 women suspected of having PJS (based on mucocutaneous pigmentation) [77]. Multiple studies indicated cases with bilateral BC, and one case of a male PJS patient developing BC was described [11,12,[76][77][78].…”

Section: Breast Managementmentioning

confidence: 99%

“…Lipsa et al reported BC in 4/7 women with a PV in STK11 and in 5/8 women suspected of having PJS (based on mucocutaneous pigmentation) [77]. Multiple studies indicated cases with bilateral BC, and one case of a male PJS patient developing BC was described [11,12,[76][77][78]. A few studies stratified the risk of breast cancer in female PJS patients; BC risk was 5-12.7% at age 40, 11-24% at age 50, and up to 24-54% at age 60-70 years [11][12][13]16,24,79].…”

Section: Breast Managementmentioning

confidence: 99%

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The Management of Peutz–Jeghers Syndrome: European Hereditary Tumour Group (EHTG) Guideline

Wagner

Aretz

Auranen

et al. 2021

JCM

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The scientific data to guide the management of Peutz–Jeghers syndrome (PJS) are sparse. The available evidence has been reviewed and discussed by diverse medical specialists in the field of PJS to update the previous guideline from 2010 and formulate a revised practical guideline for colleagues managing PJS patients. Methods: Literature searches were performed using MEDLINE, Embase, and Cochrane. Evidence levels and recommendation strengths were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). A Delphi process was followed, with consensus being reached when ≥80% of the voting guideline committee members agreed. Recommendations and statements: The only recent guidelines available were for gastrointestinal and pancreatic management. These were reviewed and endorsed after confirming that no more recent relevant papers had been published. Literature searches were performed for additional questions and yielded a variable number of relevant papers depending on the subject addressed. Additional recommendations and statements were formulated. Conclusions: A decade on, the evidence base for recommendations remains poor, and collaborative studies are required to provide better data about this rare condition. Within these restrictions, multisystem, clinical management recommendations for PJS have been formulated.

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Chemotolerance of Breast Cancer and Its Management by Personalized Medicine

Rawi

Malik

Masood

2022

Breast Cancer: From Bench to Personalized Medicine

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Novel germline STK11 variants and breast cancer phenotype identified in an Indian cohort of Peutz–Jeghers syndrome

Cited by 17 publications

References 38 publications

Distinct promoter methylation patterns of LKB1 in the hamartomatous polyps of Peutz-Jeghers syndrome and its potential in gastrointestinal malignancy prediction

Distinct promoter methylation patterns of LKB1 in the hamartomatous polyps of Peutz-Jeghers syndrome and its potential in gastrointestinal malignancy prediction

The Management of Peutz–Jeghers Syndrome: European Hereditary Tumour Group (EHTG) Guideline

Chemotolerance of Breast Cancer and Its Management by Personalized Medicine

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