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Cancers Originate from Somatic Mutations in a Single Cell

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...

Cancers Originate from Somatic Mutations in a Single Cell

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...

Interactions Between Signaling Pathways

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...

Tumor Progression

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...

Cancer

Cancer

Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.

Adaptive Mechanisms in Cancer Cells

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...

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Comparative Lesions Analysis Through a Targeted Sequencing Approach

Comparative Lesions Analysis Through a Targeted Sequencing Approach

Published on: November 5, 2019

Diversos patrones de mutación somática y alteraciones de las vías en los cánceres humanos.

Zhengyan Kan¹, Bijay S Jaiswal, Jeremy Stinson

¹Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.

|July 30, 2010

Resumen

Este estudio identificó 2.576 mutaciones somáticas en 1.507 genes en 441 tumores de cáncer. Los genes mutados clave, incluidos GNAS y MAP2K4, ofrecen objetivos potenciales para nuevas terapias contra el cáncer.

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Área de la Ciencia:

La genómica es la genómica.
Biología del cáncer Biología del cáncer.
Oncología Molecular Oncología Molecular

Sus antecedentes:

Las mutaciones somáticas en los genomas del cáncer son cruciales para comprender los mecanismos de la enfermedad.
El desarrollo de terapias dirigidas requiere una caracterización genómica integral.

Objetivo del estudio:

Identificar y caracterizar sistemáticamente las mutaciones somáticas en los principales tipos de cáncer humano.
Descubrir nuevos objetivos farmacológicos para la terapia del cáncer.

Principales métodos:

Secuenciación de todo el genoma de 441 tumores (mama, pulmón, ovario, próstata).
Identificación y análisis estadístico de mutaciones somáticas y alteraciones en el número de copias.
Estudios funcionales de los principales genes mutados (GNAO1, MAP2K4).

Principales resultados:

Se identificaron 2.576 mutaciones somáticas en 1.507 genes codificantes.
Se encontraron variaciones significativas en las tasas de mutación y los conjuntos de genes en todos los tipos / subtipos de tumores.
Descubrieron 77 genes significativamente mutados (por ejemplo, GRM8, BAI3, AGTRL1, LPHN3) y 35 genes alterados adicionales (por ejemplo, GNAS).
Papel funcional demostrado de los mutantes GNAO1 y MAP2K4 en la oncogénesis.

Conclusiones:

El panorama mutacional de los cánceres humanos es diverso y específico para cada subtipo.
Se identificaron numerosos objetivos terapéuticos potenciales, incluidos los receptores acoplados a la proteína G y los componentes de la vía de señalización.
Destaca el papel ampliado de las subunidades G-alfa en el desarrollo del cáncer.