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International Journal of Clinical Oncology
Erschienen in: International Journal of Clinical Oncology 9/2019

04.07.2019 | Invited Review Article

Genetic and genomic basis of the mismatch repair system involved in Lynch syndrome

verfasst von: Kazuo Tamura, Motohide Kaneda, Mashu Futagawa, Miho Takeshita, Sanghyuk Kim, Mina Nakama, Norihito Kawashita, Junko Tatsumi-Miyajima

Erschienen in: International Journal of Clinical Oncology | Ausgabe 9/2019

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Abstract

Lynch syndrome is a cancer-predisposing syndrome inherited in an autosomal-dominant manner, wherein colon cancer and endometrial cancer develop frequently in the family, it results from a loss-of-function mutation in one of four different genes (MLH1, MSH2, MSH6, and PMS2) encoding mismatch repair proteins. Being located immediately upstream of the MSH2 gene, EPCAM abnormalities can affect MSH2 and cause Lynch syndrome. Mismatch repair proteins are involved in repairing of incorrect pairing (point mutations and deletion/insertion of simple repetitive sequences, so-called microsatellites) that can arise during DNA replication. MSH2 forms heterodimers with MSH6 or MSH3 (MutSα, MutSβ, respectively) and is involved in mismatch-pair recognition and initiation of repair. MLH1 forms a complex with PMS2, and functions as an endonuclease. If the mismatch repair system is thoroughly working, genome integrity is maintained completely. Lynch syndrome is a state of mismatch repair deficiency due to a monoallelic abnormality of any mismatch repair genes. The phenotype indicating the mismatch repair deficiency can be frequently shown as a microsatellite instability in tumors. Children with germline biallelic mismatch repair gene abnormalities were reported to develop conditions such as gastrointestinal polyposis, colorectal cancer, brain cancer, leukemia, etc., and so on, demonstrating the need to respond with new concepts in genetic counseling. In promoting cancer genome medicine in a new era, such as by utilizing immune checkpoints, it is important to understand the genetic and genomic molecular background, including the status of mismatch repair deficiency.
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Metadaten
Titel
Genetic and genomic basis of the mismatch repair system involved in Lynch syndrome
verfasst von
Kazuo Tamura
Motohide Kaneda
Mashu Futagawa
Miho Takeshita
Sanghyuk Kim
Mina Nakama
Norihito Kawashita
Junko Tatsumi-Miyajima
Publikationsdatum
04.07.2019
Verlag
Springer Singapore
Erschienen in
International Journal of Clinical Oncology / Ausgabe 9/2019
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-019-01494-y

Weitere Artikel der Ausgabe 9/2019

International Journal of Clinical Oncology 9/2019 Zur Ausgabe

Original Article

Does the extension of the type of hysterectomy contribute to the local control of endometrial cancer?

Original Article

Clinical background and outcomes of risk-reducing salpingo-oophorectomy for hereditary breast and ovarian cancers in Japan

Original Article

Elevated serum soluble interleukin-2 receptor levels increase malignancy-related risk in patients on chronic hemodialysis

Correction

Correction to: Real-world treatment of over 1600 Japanese patients with EGFR mutation-positive non-small cell lung cancer with daily afatinib

Original Article

Carbon-ion radiotherapy for lymph node oligo-recurrence: a multi-institutional study by the Japan Carbon-Ion Radiation Oncology Study Group (J-CROS)

Original Article

Prognostic value of serum C-reactive protein level prior to second-line treatment in intermediate risk metastatic renal cell carcinoma patients

Neu im Fachgebiet Onkologie

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

28.05.2024 Nebenwirkungen der Krebstherapie Nachrichten

Kardiotoxische Nebenwirkungen einer Therapie mit Immuncheckpointhemmern mögen selten sein – wenn sie aber auftreten, wird es für Patienten oft lebensgefährlich. Voruntersuchung und Monitoring sind daher obligat.

Positiver FIT: Die Ursache liegt nicht immer im Dickdarm

27.05.2024 Blut im Stuhl Nachrichten

Immunchemischer Stuhltest positiv, Koloskopie negativ – in solchen Fällen kann die Blutungsquelle auch weiter proximal sitzen. Ein Forschungsteam hat nachgesehen, wie häufig und in welchen Lokalisationen das der Fall ist.

Mammakarzinom: Brustdichte beeinflusst rezidivfreies Überleben

26.05.2024 Mammakarzinom Nachrichten

Frauen, die zum Zeitpunkt der Brustkrebsdiagnose eine hohe mammografische Brustdichte aufweisen, haben ein erhöhtes Risiko für ein baldiges Rezidiv, legen neue Daten nahe.

Mehr Lebenszeit mit Abemaciclib bei fortgeschrittenem Brustkrebs?

24.05.2024 Mammakarzinom Nachrichten

In der MONARCHE-3-Studie lebten Frauen mit fortgeschrittenem Hormonrezeptor-positivem, HER2-negativem Brustkrebs länger, wenn sie zusätzlich zu einem nicht steroidalen Aromatasehemmer mit Abemaciclib behandelt wurden; allerdings verfehlte der numerische Zugewinn die statistische Signifikanz.

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