Changes in cancer-critical genes/proteins in different human tumors were analyzed. Gene amplification or deregulation leads to increased expression (X), while mutations, deletions, or recombination leads to inactivation (Y).

Column X	Column Y
A. E-cadherin, Smad4, Ras, Myc	i. PTEN, APC, AKT, Her2
B. AKT, Ras, Myc, Her2	ii. PTEN, E-cadherin, APC, Smad4
C. AKT, Ras, Myc, Smad4	iii. PTEN, E-cadherin, APC, Her2
D. E-cadherin, AKT, Ras, Myc	iv. Her2, PTEN, APC, Smad4

Which combination of X and Y is most likely to be found in the tumors?

Correct option is B

Option B-ii:

• AKT, Ras, Myc, Her2 with PTEN, E-cadherin, APC, Smad4
  This combination makes sense because:

  • AKT, Ras, Myc, and Her2 are genes commonly upregulated in cancer. These genes contribute to tumorigenesis and increased cell growth and survival.

  • On the other hand, the inactivated genes PTEN, E-cadherin, APC, and Smad4 are tumor suppressors. Mutations, deletions, or recombination of these genes lead to their inactivation, contributing to cancer progression.

  • Specifically, PTEN is a tumor suppressor gene that is often deleted or mutated in cancer; E-cadherin is involved in cell adhesion, and its loss contributes to tumor metastasis; APC and Smad4 are also tumor suppressor genes often inactivated in various cancers.

Why Option B-ii is correct:

• AKT, Ras, Myc, and Her2 are often overexpressed or amplified in various cancers, driving cell growth and survival.

• PTEN, E-cadherin, APC, and Smad4 are inactivated by mutations, deletions, or recombination events, making this combination the most plausible for cancer-critical genes.

Other Options:

Option A-i:

• E-cadherin, Smad4, Ras, Myc with PTEN, APC, AKT, Her2
  This combination does not fit because E-cadherin, Smad4, Ras, and Myc are not typically all upregulated in the same tumor. Furthermore, the response of PTEN, APC, and AKT being inactivated by mutations is unlikely to match this combination.

Option C-iii:

• AKT, Ras, Myc, Smad4 with PTEN, E-cadherin, APC, Her2
  Smad4 is typically a tumor suppressor gene, not one that is overexpressed in tumors. Therefore, this option doesn’t make sense in the context of gene deregulation.

Option D-iv:

• E-cadherin, AKT, Ras, Myc with Her2, PTEN, APC, Smad4
  This combination is unlikely because E-cadherin is usually downregulated in cancer, while AKT, Ras, and Myc are typically upregulated. Therefore, this is not a good match for gene deregulation leading to cancer.