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Related Concept Videos

Tumor Progression02:07

Tumor Progression

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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...
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  1. Home
  3. Evolutionary Pathways In Early-stage, Non-myoinvasive Endometrioid Endometrial Cancers Of No Specific Molecular Profile.
  1. Home
  3. Evolutionary Pathways In Early-stage, Non-myoinvasive Endometrioid Endometrial Cancers Of No Specific Molecular Profile.

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Evolutionary pathways in early-stage, non-myoinvasive endometrioid endometrial cancers of no specific molecular

Sara Moufarrij1, Yulia Lakhman2, Carol Aghajanian3

  • 1Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.

Gynecologic Oncology
|November 7, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

Early-stage endometrioid endometrial cancers (ECs) with no specific molecular profile (NSMP) exhibit diverse genomic alterations, including frequent PTEN, ARID1A, and PIK3CA mutations. These genetic changes suggest multiple tumor evolution pathways in early EC development.

Keywords:
Endometrial carcinomaTumor evolutionTumor heterogeneity

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Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • Endometrioid endometrial cancer (EC) is a common gynecologic malignancy.
  • Understanding the genomic landscape of early-stage EC is crucial for defining tumor evolution.
  • The no specific molecular profile (NSMP) subtype represents a distinct molecular category within EC.

Purpose of the Study:

  • To characterize the genomic landscape of FIGO 2009 stage IA, non-myometrial invasive endometrioid endometrial cancers (ECs) of no specific molecular profile (NSMP).
  • To identify the earliest driver genetic alterations in these early-stage ECs.
  • To define the subsequent tumor evolution pathways in NSMP ECs.

Main Methods:

  • Targeted tumor-normal sequencing of 171 early-stage (FIGO 2009 stage IA), non-myoinvasive endometrioid NSMP ECs.
  • Dichotomization of ECs into low- and high-volume disease based on a 1.8 cm³ cutoff.
  • Determination of cancer cell fractions (CCF) for somatic mutations.

    • Main Results:

    • The majority (81%) of the 171 identified ECs were FIGO grade 1.
    • Frequent mutations were observed in PTEN (80%), ARID1A (52%), PIK3CA (52%), CTNNB1 (39%), PIK3R1 (37%), and KRAS (29%).
    • Unsupervised clustering revealed four distinct genomic groups based on mutation patterns and CCF, indicating multiple evolutionary trajectories.

    Conclusions:

    • Stage IA non-myoinvasive NSMP ECs display significant genomic heterogeneity.
    • These findings suggest the presence of multiple, distinct tumor evolution pathways.
    • Further research is needed to determine if this heterogeneity reflects early genomic drift.